ヒトヘルペスウイルス2型

関: herpes simplex virus 2、herpes simplex virus type 2、HSV-2、human herpesvirus 2

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/13 15:32:07」(JST)

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Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as human herpesvirus 1 and 2 (HHV-1 and HHV-2), are two members of the herpesvirus family, Herpesviridae, that infect humans.^[1] Both HSV-1 (which produces most cold sores) and HSV-2 (which produces most genital herpes) are ubiquitous and contagious. They can be spread when an infected person is producing and shedding the virus.

Symptoms of herpes simplex virus infection include watery blisters in the skin or mucous membranes of the mouth, lips or genitals.^[1] Lesions heal with a scab characteristic of herpetic disease. Sometimes, the viruses cause very mild or atypical symptoms during outbreaks. However, as neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body by becoming latent and hiding from the immune system in the cell bodies of neurons. After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron's axon to the skin, where virus replication and shedding occur and cause new sores.^[2] It is one of the most common sexually transmitted infections.^[3]

1 Transmission
2 Virology
- 2.1 Viral structure
- 2.2 Cellular entry
- 2.3 Genetic inoculation
- 2.4 Immune evasion
- 2.5 Replication
- 2.6 Latent infection
- 2.7 HSV-1 viral genome
- 2.8 HSV-2 viral genome
3 Evolution
4 Treatment
5 Alzheimer's disease
6 Multiplicity reactivation
7 Use as an anti-cancer agent
8 Use in neuronal connection tracing
9 Other related outcomes
10 Research
11 References
12 External links

Transmission

HSV-1 and -2 are transmitted by contact with an infected area of the skin during reactivations of the virus. Herpes simplex virus (HSV)-2 is periodically shed in the human genital tract, most often asymptomatically, and most sexual transmissions occur during asymptomatic shedding.^[4] Asymptomatic reactivation means that the virus causes atypical, subtle or hard to notice symptoms that are not identified as an active herpes infection. In one study, daily genital swab samples found HSV-2 at a median of 12–28% of days among those who have had an outbreak, and 10% of days among those suffering from asymptomatic infection, with many of these episodes occurring without visible outbreak ("subclinical shedding").^[5]

In another study, 73 subjects were randomized to receive valaciclovir 1 g daily or placebo for 60 days each in a 2-way crossover design. A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction, in order to compare the effect of valaciclovir 1 g once daily for 60 days versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection. The study found that valaciclovir significantly reduced shedding during subclinical days compared to placebo, showing a 71% reduction. 84% of subjects had no shedding while receiving valaciclovir versus 54% of subjects on placebo. 88% of patients treated with valaciclovir had no recognized signs or symptoms versus 77% for placebo.^[6]

For HSV-2, subclinical shedding may account for most of the transmission, and one study found that infection occurred after a median of 40 sex acts.^[5] Atypical symptoms are often attributed to other causes such as a yeast infection.^[7]^[8] HSV-1 is often acquired orally during childhood. It may also be sexually transmitted, including contact with saliva, such as kissing and mouth-to-genital contact (oral sex).^[9] HSV-2 is primarily a sexually transmitted infection, but rates of HSV-1 genital infections are increasing.^[7]

Both viruses may also be transmitted vertically during childbirth, although the real risk is very low.^[10] The risk of infection is minimal if the mother has no symptoms or exposed blisters during delivery. The risk is considerable when the mother is infected with the virus for the first time during late pregnancy.^[11]

Herpes simplex viruses can affect areas of skin exposed to contact with an infected person. An example of this is herpetic whitlow which is a herpes infection on the fingers. This was a common affliction of dental surgeons prior to the routine use of gloves when conducting treatment on patients.^{[citation needed]}

Virology

Viral structure

Play media

3D reconstruction and animation of a tail-like assembly in HSV-1 virion

3D reconstruction of Herpes simplex virus type 1 (HSV-1)

Animal herpes viruses all share some common properties. The structure of herpes viruses consists of a relatively large double-stranded, linear DNA genome encased within an icosahedral protein cage called the capsid, which is wrapped in a lipid bilayer called the envelope. The envelope is joined to the capsid by means of a tegument. This complete particle is known as the virion.^[12] HSV-1 and HSV-2 each contain at least 74 genes (or open reading frames, ORFs) within their genomes,^[13] although speculation over gene crowding allows as many as 84 unique protein coding genes by 94 putative ORFs.^[14] These genes encode a variety of proteins involved in forming the capsid, tegument and envelope of the virus, as well as controlling the replication and infectivity of the virus. These genes and their functions are summarized in the table below.

The genomes of HSV-1 and HSV-2 are complex and contain two unique regions called the long unique region (U_L) and the short unique region (U_S). Of the 74 known ORFs, U_L contains 56 viral genes, whereas U_S contains only 12.^[13] Transcription of HSV genes is catalyzed by RNA polymerase II of the infected host.^[13] Immediate early genes, which encode proteins that regulate the expression of early and late viral genes, are the first to be expressed following infection. Early gene expression follows, to allow the synthesis of enzymes involved in DNA replication and the production of certain envelope glycoproteins. Expression of late genes occurs last; this group of genes predominantly encode proteins that form the virion particle.^[13]

Five proteins from (U_L) form the viral capsid; UL6, UL18, UL35, UL38 and the major capsid protein UL19.^[12]

Cellular entry

A simplified diagram of HSV replication

Entry of HSV into the host cell involves interactions of several glycoproteins on the surface of the enveloped virus, with receptors on the surface of the host cell. The envelope covering the virus particle, when bound to specific receptors on the cell surface, will fuse with the host cell membrane and create an opening, or pore, through which the virus enters the host cell.

The sequential stages of HSV entry are analogous to those of other viruses. At first, complementary receptors on the virus and the cell surface bring the viral and cell membranes into proximity. In an intermediate state, the two membranes begin to merge, forming a hemifusion state. Finally, a stable entry pore is formed through which the viral envelope contents are introduced to the host cell.^[15] The virus can also be endocytosed after binding to the receptors, and the fusion could occur at the endosome.

In the case of a herpes virus, initial interactions occur when two viral envelope glycoprotein called glycoprotein C (gC) and glycoprotein B (gB) bind to a cell surface particle called heparan sulfate. Next, the major receptor binding protein, glycoprotein D (gD), binds specifically to at least one of three known entry receptors.^[16] These cell receptors include herpesvirus entry mediator (HVEM), nectin-1 and 3-O sulfated heparan sulfate. The receptor provides a strong, fixed attachment to the host cell. These interactions bring the membrane surfaces into mutual proximity and allow for other glycoproteins embedded in the viral envelope to interact with other cell surface molecules. Once bound to the HVEM, gD changes its conformation and interacts with viral glycoproteins H (gH) and L (gL), which form a complex. The interaction of these membrane proteins results in the hemifusion state. Afterward, gB interaction with the gH/gL complex creates an entry pore for the viral capsid.^[15] gB interacts with glycosaminoglycans on the surface of the host cell.^{[citation needed]}

Genetic inoculation

After the viral capsid enters the cellular cytoplasm, it is transported to the cell nucleus. Once attached to the nucleus at a nuclear entry pore, the capsid ejects its DNA contents via the capsid portal. The capsid portal is formed by twelve copies of portal protein, UL6, arranged as a ring; the proteins contain a leucine zipper sequence of amino acids which allow them to adhere to each other.^[17] Each icosahedral capsid contains a single portal, located in one vertex.^[18]^[19] The DNA exits the capsid in a single linear segment.^[20]

Immune evasion

HSV evades the immune system through interference with MHC class I antigen presentation on the cell surface, by blocking TAP or the transporter associated with antigen processing induced by the secretion of ICP-47 by HSV.^[21] In the host cell, TAP transports digested viral antigen epitope peptides from the cytosol to the endoplasmic reticulum, allowing these epitopes to be combined with MHC class I molecules and presented on the surface of the cell. Viral epitope presentation with MHC class I is a requirement for activation of cytotoxic T-lymphocytes (CTLs), the major effectors of the cell-mediated immune response against virally-infected cells. ICP-47 prevents initiation of a CTL-response against HSV, allowing the virus to survive for a protracted period in the host.

Replication

Micrograph showing the viral cytopathic effect of HSV (multi-nucleation, ground glass chromatin).

Following infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, are produced. Research using flow cytometry on another member of the herpes virus family, Kaposi's sarcoma-associated herpesvirus, indicates the possibility of an additional lytic stage, delayed-late.^[22] These stages of lytic infection, particularly late lytic, are distinct from the latency stage. In the case of HSV-1, no protein products are detected during latency, whereas they are detected during the lytic cycle.

The early proteins transcribed are used in the regulation of genetic replication of the virus. On entering the cell, an α-TIF protein joins the viral particle and aids in immediate-early transcription. The virion host shutoff protein (VHS or UL41) is very important to viral replication.^[23] This enzyme shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, and regulates gene expression of viral proteins. The viral genome immediately travels to the nucleus but the VHS protein remains in the cytoplasm.^[24]^[25]

The late proteins form the capsid and the receptors on the surface of the virus. Packaging of the viral particles — including the genome, core and the capsid - occurs in the nucleus of the cell. Here, concatemers of the viral genome are separated by cleavage and are placed into pre-formed capsids. HSV-1 undergoes a process of primary and secondary envelopment. The primary envelope is acquired by budding into the inner nuclear membrane of the cell. This then fuses with the outer nuclear membrane releasing a naked capsid into the cytoplasm. The virus acquires its final envelope by budding into cytoplasmic vesicles.^[26]

Latent infection

HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia.^[1] HSV-1 tends to reside in the trigeminal ganglia, while HSV-2 tends to reside in the sacral ganglia, but these are tendencies only, not fixed behavior. During latent infection of a cell, HSVs express Latency Associated Transcript (LAT) RNA. LAT regulates the host cell genome and interferes with natural cell death mechanisms. By maintaining the host cells, LAT expression preserves a reservoir of the virus, which allows subsequent, usually symptomatic, periodic recurrences or "outbreaks" characteristic of non-latency. Whether or not recurrences are symptomatic, viral shedding occurs to infect a new host. A protein found in neurons may bind to herpes virus DNA and regulate latency. Herpes virus DNA contains a gene for a protein called ICP4, which is an important transactivator of genes associated with lytic infection in HSV-1.^[27] Elements surrounding the gene for ICP4 bind a protein known as the human neuronal protein Neuronal Restrictive Silencing Factor (NRSF) or human Repressor Element Silencing Transcription Factor (REST). When bound to the viral DNA elements, histone deacetylation occurs atop the ICP4 gene sequence to prevent initiation of transcription from this gene, thereby preventing transcription of other viral genes involved in the lytic cycle.^[27]^[28] Another HSV protein reverses the inhibition of ICP4 protein synthesis. ICP0 dissociates NRSF from the ICP4 gene and thus prevents silencing of the viral DNA.^[29]

The virus can be reactivated by illnesses such as colds and influenza, eczema, emotional and physical stress, gastric upset, fatigue or injury, by menstruation and possibly exposure to bright sunlight. Genital Herpes may be reactivated by friction.^{[citation needed]}

HSV-1 viral genome

The open reading frames (ORFs) of HSV-1^[13]^[30]
Gene	Protein	Function/description	Gene	Protein	Function/description
UL1	Glycoprotein L [1]	Surface and membrane	UL38	UL38; VP19C [2]	Capsid assembly and DNA maturation
UL2	UL2 [3]	Uracil-DNA glycosylase	UL39	UL39; RR-1; ICP6 [4]	Ribonucleotide reductase (Large subunit)
UL3	UL3 [5]	unknown	UL40	UL40; RR-2 [6]	Ribonucleotide reductase (Small subunit)
UL4	UL4 [7]	unknown	UL41	UL41; VHS [8]	Tegument protein; Virion host shutoff^[23]
UL5	UL5 [9]	DNA replication	UL42	UL42 [10]	DNA polymerase processivity factor
UL6	Portal protein U_L-6	Twelve of these proteins constitute the capsid portal ring through which DNA enters and exits the capsid.^[17]^[18]^[19]	UL43	UL43 [11]	Membrane protein
UL7	UL7 [12]	Virion maturation	UL44	Glycoprotein C [13]	Surface and membrane
UL8	UL8 [14]	DNA virus helicase-primase complex-associated protein	UL45	UL45 [15]	Membrane protein; C-type lectin^[31]
UL9	UL9 [16]	Replication origin-binding protein	UL46	VP11/12 [17]	Tegument proteins
UL10	Glycoprotein M [18]	Surface and membrane	UL47	UL47; VP13/14 [19]	Tegument protein
UL11	UL11 [20]	virion exit and secondary envelopment	UL48	VP16 (Alpha-TIF) [21]	Virion maturation; activate IE genes by interacting with the cellular transcription factors Oct-1 and HCF. Binds to the sequence ^5'TAATGARAT^3'.
UL12	UL12 [22]	Alkaline exonuclease	UL49	UL49A [23]	Envelope protein
UL13	UL13 [24]	Serine-threonine protein kinase	UL50	UL50 [25]	dUTP diphosphatase
UL14	UL14 [26]	Tegument protein	UL51	UL51 [27]	Tegument protein
UL15	Terminase [28]	Processing and packaging of DNA	UL52	UL52 [29]	DNA helicase/primase complex protein
UL16	UL16 [30]	Tegument protein	UL53	Glycoprotein K [31]	Surface and membrane
UL17	UL17 [32]	Processing and packaging DNA	UL54	IE63; ICP27 [33]	Transcriptional regulation
UL18	VP23 [34]	Capsid protein	UL55	UL55 [35]	Unknown
UL19	VP5 [36]	Major capsid protein	UL56	UL56 [37]	Unknown
UL20	UL20 [38]	Membrane protein	US1	ICP22; IE68 [39]	Viral replication
UL21	UL21 [40]	Tegument protein^[32]	US2	US2 [41]	Unknown
UL22	Glycoprotein H [42]	Surface and membrane	US3	US3 [43]	Serine/threonine-protein kinase
UL23	Thymidine kinase [44]	Peripheral to DNA replication	US4	Glycoprotein G [45]	Surface and membrane
UL24	UL24 [46]	unknown	US5	Glycoprotein J [47]	Surface and membrane
UL25	UL25 [48]	Processing and packaging DNA	US6	Glycoprotein D [49]	Surface and membrane
UL26	P40; VP24; VP22A [50]	Capsid protein	US7	Glycoprotein I [51]	Surface and membrane
UL27	Glycoprotein B [52]	Surface and membrane	US8	Glycoprotein E [53]	Surface and membrane
UL28	ICP18.5 [54]	Processing and packaging DNA	US9	US9 [55]	Tegument protein
UL29	UL29; ICP8 [56]	Major DNA-binding protein	US10	US10 [57]	Capsid/Tegument protein
UL30	DNA polymerase [58]	DNA replication	US11	US11; Vmw21 [59]	Binds DNA and RNA
UL31	UL31 [60]	Nuclear matrix protein	US12	ICP47; IE12 [61]	Inhibits MHC class I pathway by preventing binding of antigen to TAP
UL32	UL32 [62]	Envelope glycoprotein	RS1	ICP4; IE175 [63]	Major transcriptional activator. Essential for progression beyond the immediate-early phase of infection. IEG transcription repressor.
UL33	UL33 [64]	Processing and packaging DNA	ICP0	ICP0; IE110; α0 [65]	E3 ubiquitin ligase that activates viral gene transcription by opposing chromatinization of the viral genome and counteracts intrinsic- and interferon-based antiviral responses.^[33]
UL34	UL34 [66]	Inner nuclear membrane protein	LRP1	LRP1 [67]	Latency-related protein
UL35	VP26 [68]	Capsid protein	LRP2	LRP2 [69]	Latency-related protein
UL36	UL36 [70]	Large tegument protein	RL1	RL1; ICP34.5 [71]	Neurovirulence factor. Antagonizes PKR by de-phosphorylating eIF4a. Binds to BECN1 and inactivates autophagy.
UL37	UL37 [72]	Capsid assembly	LAT	none [73]	Latency-associated transcript

HSV-2 viral genome

ORF or feature	Comments
a sequence	Terminal direct repeat
RL1	Neurovirulence factor
Exon 1
Exon 2
RL2	Immediate-early protein; modulator of cell state and gene expression
Exon 1
Exon 2
Exon 3
LAT	LAT initiation site; poly(A) site in circularized genome
Start of UL
UL1	Virion surface glycoprotein L
UL2	Uracil-DNA glycosylase
UL3	Nuclear phosphoprotein
UL4
UL5	Component of DNA helicase-primase
UL6	Minor capsid protein
UL7
UL8	Component of DNA helicase-primase
UL9	Ori binding protein
UL10	Virion membrane glycoprotein M
UL11	Myristylated tegument protein
UL12	DNase
UL13	Protein kinase; tegument protein
UL14
UL15	Role in DNA packaging
Exon 1
Exon 2
UL16	Proposed initiator CTG codon
UL17
UL18	Capsid protein
UL19	Major capsid protein (start ATG quoted is second possible)
UL20	Virion membrane protein
UL21	Tegument protein
UL22	Virion membrane glycoprotein H
UL23	Thymidine kinase (2 possible poly(A) sites)
UL24
UL25	Virion protein; roles in penetration and virus assembly
UL26	Capsid maturation protease
UL26.5	Capsid assembly protein
UL27	Virion membrane glycoprotein B
UL28	Role in DNA packaging
UL29	Single-stranded DNA binding protein
OriL	Origin of DNA replication; location of palindrome given
UL30	DNA polymerase catalytic subunit
UL31
UL32
UL33	Role in DNA packaging
UL34	Membrane-associated phosphoprotein
UL35	Capsid protein
UL36	Very large tegument protein (reiterations omitted for calculation of Ka and Ks)
UL37	Tegument protein
UL38	Capsid protein
UL39	Ribonucleotide reductase large subunit
UL40	Ribonucleotide reductase small subunit
UL41	Tegument protein; host shutoff factor; defective in HSV-2 (HG52) (see text)
UL42	DNA polymerase subunit
UL43	Probable membrane protein
UL44	Virion membrane glycoprotein C
UL45	Tegument/envelope protein
UL46	Tegument protein
UL47	Tegument protein
UL48	Tegument protein; transactivator of immediate-early genes
UL49	Tegument protein
UL49A	Probable virion membrane protein
UL50	Deoxyuridine triphosphatase
UL51
UL52	Component of DNA helicase-primase; ATG initiator codon quoted corresponds to HSV-1 (see text)
UL53	Membrane glycoprotein K
UL54	Immediate-early protein; posttranslational regulator of gene expression
UL55
UL56
Start of IRL
LAT	LAT initiation and poly(A) sites
RL2	Immediate-early protein; modulator of cell state and gene expression
Exon 3
Exon 2
Exon 1
RL1	Neurovirulence factor
Exon 2
Exon 1
a′ sequence	Opposite-sense copy of sequence directly repeated at genomic termini
RS1	Immediate-early protein; transcriptional regulator
OriS	Origin of DNA replication; limits given are for directly repeated 138 nucleotides
Start of US
US1	Immediate-early protein; intron in 5′ noncoding region
US2
US3	Protein kinase
US4	Virion membrane glycoprotein G
US5	Putative membrane glycoprotein J
US6	Virion membrane glycoprotein D
US7	Virion membrane glycoprotein I
US8	Virion membrane glycoprotein E
US8A	Nucleolar protein
US9	Tegument protein
US10	Virion protein
US11	Nucleolar, RNA binding protein
US12	Immediate-early protein; inhibitor of antigen presentation; intron in 5′ noncoding region
Start of TRS
OriS	Origin of DNA replication; limits given are for directly repeated 138 nucleotides
RS1	Immediate-early protein; transcriptional regulator
a sequence	Terminal direct repeat

Evolution

The herpes simplex 1 genomes can be classified into six clades.^[34] Four of these occur in East Africa, one in East Asia and one in Europe and North America. This suggests that the virus may have originated in East Africa. The most recent common ancestor of the Eurasian strains appears to have evolved ~60,000 years ago.^[35] The East Asian HSV-1 isolates have an unusual pattern that is currently best explained by the two waves of migration responsible for the peopling of Japan.^{[citation needed]}

The mutation rate has been estimated to be ~1.38×10⁻⁷ substitutions/site/year.^[34] In clinical setting, the mutations in either the thymidine kinase gene or DNA polymerase gene has caused resistance to aciclovir. However, most of the mutations occur in the thymidine kinase gene rather than the DNA polymerase gene.^[36]

Treatment

For more details on treatment of herpes simplex virus, see Herpes simplex.

Herpes viruses establish lifelong infections, and the virus cannot yet be eradicated from the body. Treatment usually involves general-purpose antiviral drugs that interfere with viral replication, reduce the physical severity of outbreak-associated lesions, and lower the chance of transmission to others. Studies of vulnerable patient populations have indicated that daily use of antivirals such as aciclovir^[37] and valaciclovir can reduce reactivation rates.^[8]

Alzheimer's disease

In the presence of a certain gene variation (APOE-epsilon4 allele carriers), a possible link between HSV-1 (i.e., the virus that causes cold sores or oral herpes) and Alzheimer's disease was reported in 1979.^[38] HSV-1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer's disease.^[39] This research identifies HSVs as the pathogen most clearly linked to the establishment of Alzheimer’s.^[40] According to a study done in 1997, without the presence of the gene allele, HSV-1 does not appear to cause any neurological damage or increase the risk of Alzheimer’s.^[41] However, a more recent prospective study published in 2008 with a cohort of 591 people showed a statistically significant difference between patients with antibodies indicating recent reactivation of HSV and those without these antibodies in the incidence of Alzheimer's disease, without direct correlation to the APOE-epsilon4 allele.^[42] It should be noted that the trial had a small sample of patients who did not have the antibody at baseline, so the results should be viewed as highly uncertain. In 2011 Manchester University scientists showed that treating HSV1-infected cells with antiviral agents decreased the accumulation of β-amyloid and P-tau, and also decreased HSV-1 replication.^[43]

Multiplicity reactivation

Multiplicity reactivation (MR) is the process by which viral genomes containing inactivating damage interact within an infected cell to form a viable viral genome. MR was originally discovered with the bacterial virus bacteriophage T4, but was subsequently also found with pathogenic viruses including influenza virus, HIV-1, adenovirus simian virus 40, vaccinia virus, reovirus, poliovirus and herpes simplex virus.^[44]

When HSV particles are exposed to doses of a DNA damaging agent that would be lethal in single infections, but are then allowed to undergo multiple infection (i.e. two or more viruses per host cell), MR is observed. Enhanced survival of HSV-1 due to MR occurs upon exposure to different DNA damaging agents, including methyl methanesulfonate,^[45] trimethylpsoralen (which causes inter-strand DNA cross-links),^[46]^[47] and UV light.^[48] After treatment of genetically marked HSV with trimethylpsoralen, recombination between the marked viruses increases, suggesting that trimethylpsoralen damages stimulate recombination.^[46] MR of HSV appears to partially depend on the host cell recombinational repair machinery since skin fibroblast cells defective in a component of this machinery (i.e. cells from Bloom’s syndrome patients) are deficient in MR.^[48] These observations suggest that MR in HSV infections involves genetic recombination between damaged viral genomes resulting in production of viable progeny viruses. HSV-1, upon infecting host cells, induces inflammation and oxidative stress.^[49] Thus it appears that the HSV genome may be subjected to oxidative DNA damage during infection, and that MR may enhance viral survival and virulence under these conditions.

Use as an anti-cancer agent

Herpes simplex virus is considered as a potential therapy for cancer and has been extensively clinically tested to assess its oncolytic (cancer killing) ability.^[50] Interim overall survival data from Amgen's phase 3 trial of a genetically-attenuated herpes virus suggests efficacy against melanoma.^[51]

Use in neuronal connection tracing

Herpes simplex virus is also used as a transneuronal tracer defining connections among neurons by virtue of traversing synapses.^[52]

Other related outcomes

Herpes simplex virus is likely the most common cause of Mollaret's meningitis,^[53] and, in worse case scenarios, can lead to a potentially fatal case of herpes simplex encephalitis.^[54]

Research

There exist commonly used vaccines to some herpesviruses, but only veterinary, such as HVT/LT (Turkey herpesvirus vector laryngotracheitis vaccine), interestingly however, it prevents atherosclerosis (which histologically mirrors atherosclerosis in humans) in target animals vaccinated.^[55]^[56]

Vaccine	Company	Lead Researcher	Vaccine Type	Status
HSV-2 ICP0‾ HSV-2 0ΔNLS^[57]	Rational Vaccines RVX	William Halford^[58]	Live, Attenuated Interferon Sensitive	NA
dl5-29 / ACAM-529 / HSV-529	Sanofi Pastuer	David Knipe^[59]	Live, Attenuated Replication-Defective HSV	Phase I
Admedus^[60]	Admedus	Ian Frazier	DNA vaccine: codon optimized	Phase II
HerpV	Agenus	?	Peptide vaccine/QS-21 adjuvant	?
Gen-003	Genocea	?	Sub Unit gD2/ICP4 with Matrix M2 adjuvant	Phase II
Vical	Vical	?	DNA Vaccine: gD2+UL46/Vaxfectin adjuvant	Phase II
Einstein	Einstein Med College	William Jacobs Jr	Live, Attenuated HSV-2 deleted in gD2	Preclinical
GV2207^[61]	GenVec	?	?	Preclinical ^[62]
Mymetics^[63]	Mymetics	?	?	Preclinical^[63]
AIC316	AICuris	?	?	?
Vitaherpavac & Herpovax	?	?	?	?
NE-HSV2^[64]	NanoBio^[65]	?	?	Preclinical
GeneVax prime/^[66]	Profectus BioSciences	?	?	?
Biomedical Research Models	?	?	?	?
Tomegavax	?	?	?	?
Herpevac	GlaxoSmithKline	?	?	Discontinued
PaxVax^[67]	?	?	?	?
Amgen BioVex	?	?	?	?
AuRX	?	?	Live, Attenuated	Inactive
Zostavax (VZV, shingles)	Merck	?	Live, Attenuated	In Production
Varicella (C.Pox)	Merck	?	Live, Attenuated	In Production

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^ ^a ^b ^c ^d ^e McGeoch DJ, Rixon FJ, Davison AJ (2006). "Topics in herpesvirus genomics and evolution". Virus Res. 117 (1): 90–104. doi:10.1016/j.virusres.2006.01.002. PMID 16490275.
^ Rajcáni J, Andrea V, Ingeborg R (2004). "Peculiarities of herpes simplex virus (HSV) transcription: an overview". Virus Genes. 28 (3): 293–310. doi:10.1023/B:VIRU.0000025777.62826.92. PMID 15266111.
^ ^a ^b Subramanian RP, Geraghty RJ (2007). "Herpes simplex virus type 1 mediates fusion through a hemifusion intermediate by sequential activity of glycoproteins D, H, L, and B". Proc. Natl. Acad. Sci. U.S.A. 104 (8): 2903–8. doi:10.1073/pnas.0608374104. PMC 1815279. PMID 17299053.
^ Akhtar J, Shukla D (2009). "Viral entry mechanisms: Cellular and viral mediators of herpes simplex virus entry". FEBS Journal. 276 (24): 7228–7236. doi:10.1111/j.1742-4658.2009.07402.x. PMC 2801626. PMID 19878306.
^ ^a ^b Cardone G, Winkler DC, Trus BL, Cheng N, Heuser JE, Newcomb WW, Brown JC, Steven AC (May 2007). "Visualization of the Herpes Simplex Virus Portal in situ by Cryo-electron Tomography". Virology. 361 (2): 426–34. doi:10.1016/j.virol.2006.10.047. PMC 1930166. PMID 17188319.
^ ^a ^b Trus BL, Cheng N, Newcomb WW, Homa FL, Brown JC, Steven AC (November 2004). "Structure and Polymorphism of the UL6 Portal Protein of Herpes Simplex Virus Type 1". Journal of Virology. 78 (22): 12668–71. doi:10.1128/JVI.78.22.12668-12671.2004. PMC 525097. PMID 15507654.
^ ^a ^b Nellissery JK, Szczepaniak R, Lamberti C, Weller SK (2007-06-20). "A Putative Leucine Zipper within the Herpes Simplex Virus Type 1 UL6 Protein Is Required for Portal Ring Formation". Journal Virology. 81 (17): 8868–77. doi:10.1128/JVI.00739-07. PMC 1951442. PMID 17581990.
^ Newcomb WW, Booy FP, Brown JC (2007). "Uncoating the Herpes Simplex Virus Genome". J. Mol. Biol. 370 (4): 633–42. doi:10.1016/j.jmb.2007.05.023. PMC 1975772. PMID 17540405.
^ Abbas et al (2009) Cellular and Molecular Immunology, Elsevier Inc.
^ Adang LA, Parsons CH, Kedes DH (2006). "Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection". J. Virol. 80 (20): 10073–82. doi:10.1128/JVI.01156-06. PMC 1617294. PMID 17005685.
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^ Taddeo B, Roizman B (2006). "The Virion Host Shutoff Protein (UL41) of Herpes Simplex Virus 1 Is an Endoribonuclease with a Substrate Specificity Similar to That of RNase A". J. Virol. 80 (18): 9341–5. doi:10.1128/JVI.01008-06. PMC 1563938. PMID 16940547.
^ Skepper JN, Whiteley A, Browne H, Minson A (June 2001). "Herpes Simplex Virus Nucleocapsids Mature to Progeny Virions by an Envelopment → Deenvelopment → Reenvelopment Pathway". J. Virol. 75 (12): 5697–702. doi:10.1128/JVI.75.12.5697-5702.2001. PMC 114284. PMID 11356979.
^ Granzow H, Klupp BG, Fuchs W, Veits J, Osterrieder N, Mettenleiter TC (April 2001). "Egress of Alphaherpesviruses: Comparative Ultrastructural Study". J. Virol. 75 (8): 3675–84. doi:10.1128/JVI.75.8.3675-3684.2001. PMC 114859. PMID 11264357.
^ ^a ^b Pinnoji RC, Bedadala GR, George B, Holland TC, Hill JM, Hsia SC (2007). "Repressor element-1 silencing transcription factor/neuronal restrictive silencer factor (REST/NRSF) can regulate HSV-1 immediate-early transcription via histone modification". Virol. J. 4: 56. doi:10.1186/1743-422X-4-56. PMC 1906746. PMID 17555596.
^ Bedadala GR, Pinnoji RC, Hsia SC (2007). "Early growth response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression". Cell Res. 17 (6): 546–55. doi:10.1038/cr.2007.44. PMID 17502875.
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^ Search in UniProt Knowledgebase (Swiss-Prot and TrEMBL) for: HHV1
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^ Matis J, Kúdelová M (2011). "HSV-1 ICP0: paving the way for viral replication". Future Virology. 6 (4): 421–429. doi:10.2217/fvl.11.24. PMC 3133933. PMID 21765858.
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^ Bowden R, Sakaoka H, Ward R, Donnelly P (2006). "Patterns of Eurasian HSV-1 molecular diversity and inferences of human migrations". Infect Genet Evol. 6 (1): 63–74. doi:10.1016/j.meegid.2005.01.004.
^ Hussin A, Md , Nor NS, Ibrahim N (2013). "Phenotypic and genotypic characterization of induced acyclovir-resistant clinical isolates of herpes simplex virus type 1". Antivir Res. 100: 306–313. doi:10.1016/j.antiviral.2013.09.008.
^ Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, Palmer A, Sánchez PJ, Jacobs RF, Bradley JS, Robinson JL, Shelton M, Dennehy PH, Leach C, Rathore M, Abughali N, Wright P, Frenkel LM, Brady RC, Van Dyke R, Weiner LB, Guzman-Cottrill J, McCarthy CA, Griffin J, Jester P, Parker M, Lakeman FD, Kuo H, Lee CH, Cloud GA (2011). "Oral acyclovir suppression and neurodevelopment after neonatal herpes". N. Engl. J. Med. 365 (14): 1284–92. doi:10.1056/NEJMoa1003509. PMC 3250992. PMID 21991950.
^ Middleton PJ, Petric M, Kozak M, Rewcastle NB, McLachlan DR (May 1980). "Herpes-simplex viral genome and senile and presenile dementias of Alzheimer and Pick". Lancet. 315 (8176): 1038. doi:10.1016/S0140-6736(80)91490-7. PMID 6103379.
^ Dobson CB, Itzhaki RF (1999). "Herpes simplex virus type 1 and Alzheimer's disease". Neurobiol. Aging. 20 (4): 457–65. doi:10.1016/S0197-4580(99)00055-X. PMID 10604441.
^ Pyles RB (November 2001). "The association of herpes simplex virus and Alzheimer's disease: a potential synthesis of genetic and environmental factors" (PDF). Herpes. 8 (3): 64–8. PMID 11867022.
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^ Letenneur L, Pérès K, Fleury H, Garrigue I, Barberger-Gateau P, Helmer C, Orgogozo JM, Gauthier S, Dartigues JF (2008). "Seropositivity to herpes simplex virus antibodies and risk of Alzheimer's disease: a population-based cohort study.". PLoS ONE. 3 (11): e3637. doi:10.1371/journal.pone.0003637. PMC 2572852. PMID 18982063.
^ Wozniak MA, Frost AL, Preston CM, Itzhaki RF (2011). "Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1". PLoS ONE. 6 (10): e25152. doi:10.1371/journal.pone.0025152.
^ Michod RE, Bernstein H, Nedelcu AM (2008). "Adaptive value of sex in microbial pathogens". Infection, Genetics and Evolution. 8 (3): 267–285. doi:10.1016/j.meegid.2008.01.002. PMID 18295550.
^ Das SK (1982). "Multiplicity reactivation of alkylating agent damaged herpes simplex virus (type I) in human cells". Mutation research. 105 (1–2): 15–18. doi:10.1016/0165-7992(82)90201-9. PMID 6289091.
^ ^a ^b Hall JD, Scherer K (1981). "Repair of psoralen-treated DNA by genetic recombination in human cells infected with herpes simplex virus". Cancer Research. 41 (12 Pt 1): 5033–5038. PMID 6272987.
^ Coppey J, Sala-Trepat M, Lopez B (1989). "Multiplicity reactivation and mutagenesis of trimethylpsoralen-damaged herpes virus in normal and Fanconi's anaemia cells". Mutagenesis. 4 (1): 67–71. doi:10.1093/mutage/4.1.67. PMID 2541311.
^ ^a ^b Selsky CA, Henson P, Weichselbaum RR, Little JB (1979). "Defective reactivation of ultraviolet light-irradiated herpesvirus by a Bloom's syndrome fibroblast strain". Cancer Research. 39 (9): 3392–3396. PMID 225021.
^ Valyi-Nagy T, Olson SJ, Valyi-Nagy K, Montine TJ, Dermody TS (2000). "Herpes Simplex Virus Type 1 Latency in the Murine Nervous System is Associated with Oxidative Damage to Neurons". Virology. 278 (2): 309–321. doi:10.1006/viro.2000.0678. PMID 11118355.
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External links

Genital Herpes - Public Health Agency of Canada
Herpes simplex: Host viral protein interactions: A database of HSV-1 interacting host proteins
3D macromolecular structures of the Herpes simplex virus archived in the EM Data Bank(EMDB)

UpToDate Contents

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1. ヒトヘルペスウイルス7感染 human herpesvirus 7 infection
2. 造血細胞移植レシピエントにおけるヒトヘルペスウイルス6感染 human herpesvirus 6 infection in hematopoietic cell transplant recipients
3. ヒトヘルペスウイルス6型感染症のウイルス学、病因、および疫学 virology pathogenesis and epidemiology of human herpesvirus 6 infection
4. 小児におけるヒトヘルペスウイルス6感染：臨床症状、診断および治療 human herpesvirus 6 infection in children clinical manifestations diagnosis and treatment
5. ヒトヘルペスウイルス8感染のウイルス学、疫学、および伝播 virology epidemiology and transmission of human herpesvirus 8 infection

English Journal

Occurrence of viral DNA in paired samples of corneal rim and cornea preservation fluid.

Broniek G1, Langwińska-Wośko E1,2, Sybilska M1, Szaflik JP1,2, Przybylski M3, Wróblewska M4,5.
Journal of medical virology.J Med Virol.2016 Sep 2. doi: 10.1002/jmv.24675. [Epub ahead of print]
Corneal transplants have one of the highest success rates amongst all transplantological procedures. Corneas intended for transplantation are stored in a preservation fluid, which is then tested for bacterial and fungal infections. Amongst all analyses of infectious complications following corneal t
PMID 27588373

CLINICAL PRACTICE. Genital Herpes.

Gnann JW Jr1, Whitley RJ1.
The New England journal of medicine.N Engl J Med.2016 Aug 18;375(7):666-74. doi: 10.1056/NEJMcp1603178.
PMID 27532832

Seropositivity of neurotropic infectious agents in first-episode schizophrenia patients and the relationship with positive and negative symptoms.

Bolu A1, Oznur T, Tok D, Balikci A, Sener K, Celik C, Gulsun M.
Psychiatria Danubina.Psychiatr Danub.2016 Jun;28(2):132-8.
BACKGROUND: According to the neurodevelopmental model, schizophrenia is a disorder that occurs as a result of different etiologic factors during brain development, including viral infections. However, it is unclear whether these infections are related to the disease or whether they affect the sympto
PMID 27287787

Japanese Journal

HHV(2)

浅野喜造
小児感染免疫 14(1), 82-83, 2002-04-01
NAID 10012120406

Related Pictures

★リンクテーブル★

リンク元	「単純ヘルペスウイルス」「単純ヘルペスウイルス2型」「human herpesvirus 2」「ヒトヘルペスウイルス2型」「herpes simplex virus type 2」
関連記事	「HH」「H」「HHV」

「単純ヘルペスウイルス」

Herpes simplex virus
	TEM micrograph of a herpes simplex virus
Virus classification
Group:	Group I (dsDNA)
Order:	Herpesvirales
Family:	Herpesviridae
Subfamily:	Alphaherpesvirinae
Genus:	Simplexvirus
Species
	Herpes simplex virus 1 (HSV-1); Herpes simplex virus 2 (HSV-2);

　　[★]

英: herpes simplex virus, HSV
同: ヒトヘルペスウイルス
関: ウイルスヘルペスウイルス科アルファヘルペス亜属; 単純ヘルペスウイルス感染症、ウイルス

ウイルス学

ヘルペスウイルス科アルファヘルペスウイルス属に属する
エンベロープ有り
二本鎖DNA
三叉神経節(1型)、仙骨神経節(2型)に潜伏感染。
時折、再活性化される。

病原体

血清型により２種類に分かれる

単純ヘルペスウイルスI型(ヒトヘルペスウイルス1型 human herpes virus-1 HHV-1)
単純ヘルペスウイルスII型(ヒトヘルペスウイルス2型 human herpes virus-2 HHV-2)

潜伏期間

1-26日(中央値 6-8日)

単純ヘルペスウイルスI型(ヒトヘルペスウイルス1型)

口唇、目などに病巣を形成

単純ヘルペスウイルスII型(ヒトヘルペスウイルス2型)

陰部を中心とした感染

感染経路

体液感染、性的接触、経産道感染

症状

感染症

持続感染(潜伏感染)－→一生存在し続ける－→回帰発症(感冒、ストレス、日焼け、月経、末梢神経への外科的侵襲)
不顕性感染が多い？
神経向性が強い

一次増殖(局所)－－(求心性の軸索流にのって神経節へ)－→神経細胞内に潜伏感染

限局型と汎発型

新生児ヘルペス

母胎の単純ヘルペスウイルス感染による。約90%の症例が母子感染で、こののうち30％が死亡する。
母胎が性器ヘルペスに罹患してた場合、初感染の場合には50%、再感染では3%の割合で母子感染(経産道感染)が見られる。

カポジ水痘様発疹症

治療薬

アシクロビル

「単純ヘルペスウイルス2型」

　　[★]

英: herpes simplex virus type 2, herpes simplex virus 2, HSV-2
同: ヒトヘルペスウイルス2型 HHV-2
関: 単純ヘルペスウイルス

「human herpesvirus 2」

　　[★]

ヒトヘルペスウイルス2型、ヒトヘルペスウイルス2

関: herpes simplex virus 2、herpes simplex virus type 2、HHV-2、HSV-2

「ヒトヘルペスウイルス2型」

　　[★]

英: human herpesvirus 2、HHV-2
関: 単純ヘルペスウイルス2型、ヒトヘルペスウイルス2
同: HSV2

「herpes simplex virus type 2」

　　[★]

単純ヘルペスウイルス2型

関: herpes simplex virus 2、HHV-2、HSV-2、human herpesvirus 2

「HH」

　　[★]

「H」

　　[★]

「HHV」

　　[★] ヒトヘルペスウイルス

[Sherris-1] Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 555–62. ISBN 0-8385-8529-9.

[2] "Herpes simplex". DermNet NZ — New Zealand Dermatological Society. 2006-09-16. Retrieved 2006-10-15.

[StrafaceSelmin2012-3] Straface, Gianluca; Selmin, Alessia; Zanardo, Vincenzo; De Santis, Marco; Ercoli, Alfredo; Scambia, Giovanni (2012). "Herpes Simplex Virus Infection in Pregnancy". Infectious Diseases in Obstetrics and Gynecology. 2012: 1–6. doi:10.1155/2012/385697. ISSN 1064-7449.

[pmid24671939-4] Schiffer JT, Mayer BT, Fong Y, Swan DA, Wald A (2014). "Herpes simplex virus-2 transmission probability estimates based on quantity of viral shedding". J R Soc Interface. 11 (95): 20140160. doi:10.1098/rsif.2014.0160. PMID 24671939.

[Johnstonetal_2011-5] Johnston C, Koelle DM, Wald A (Dec 2011). "HSV-2: in pursuit of a vaccine.". J Clin Invest. 121 (12): 4600–9. doi:10.1172/JCI57148. PMID 22133885.

[pmid18157071-6] Sperling RS, Fife KH, Warren TJ, Dix LP, Brennan CA (March 2008). "The effect of daily valacyclovir suppression on herpes simplex virus type 2 viral shedding in HSV-2 seropositive subjects without a history of genital herpes". Sex Transm Dis. 35 (3): 286–90. doi:10.1097/OLQ.0b013e31815b0132. PMID 18157071.

[pmid18156035-7] Gupta R, Warren T, Wald A (2007). "Genital herpes". Lancet. 370 (9605): 2127–37. doi:10.1016/S0140-6736(07)61908-4. PMID 18156035.

[PMID_18186706-8] Koelle DM, Corey L (2008). "Herpes simplex: insights on pathogenesis and possible vaccines". Annual Review of Medicine. 59: 381–95. doi:10.1146/annurev.med.59.061606.095540. PMID 18186706.

[9] "EVERYTHING YOU NEED TO KNOW ABOUT HERPES".

[pmid19797284-10] Corey L, Wald A (2009). "Maternal and Neonatal HSV Infections". New England Journal of Medicine. 361 (14): 1376–85. doi:10.1056/NEJMra0807633. PMC 2780322. PMID 19797284.

[pmid17317423-11] Kimberlin DW (2007). "Herpes simplex virus infections of the newborn". Semin. Perinatol. 31 (1): 19–25. doi:10.1053/j.semperi.2007.01.003. PMID 17317423.

[pmid16814597-12] Mettenleiter TC, Klupp BG, Granzow H (2006). "Herpesvirus assembly: a tale of two membranes". Curr. Opin. Microbiol. 9 (4): 423–9. doi:10.1016/j.mib.2006.06.013. PMID 16814597.

[pmid16490275-13] McGeoch DJ, Rixon FJ, Davison AJ (2006). "Topics in herpesvirus genomics and evolution". Virus Res. 117 (1): 90–104. doi:10.1016/j.virusres.2006.01.002. PMID 16490275.

[pmid15266111-14] Rajcáni J, Andrea V, Ingeborg R (2004). "Peculiarities of herpes simplex virus (HSV) transcription: an overview". Virus Genes. 28 (3): 293–310. doi:10.1023/B:VIRU.0000025777.62826.92. PMID 15266111.

[Subramanian_17299053-15] Subramanian RP, Geraghty RJ (2007). "Herpes simplex virus type 1 mediates fusion through a hemifusion intermediate by sequential activity of glycoproteins D, H, L, and B". Proc. Natl. Acad. Sci. U.S.A. 104 (8): 2903–8. doi:10.1073/pnas.0608374104. PMC 1815279. PMID 17299053.

[16] Akhtar J, Shukla D (2009). "Viral entry mechanisms: Cellular and viral mediators of herpes simplex virus entry". FEBS Journal. 276 (24): 7228–7236. doi:10.1111/j.1742-4658.2009.07402.x. PMC 2801626. PMID 19878306.

[pmid17188319-17] Cardone G, Winkler DC, Trus BL, Cheng N, Heuser JE, Newcomb WW, Brown JC, Steven AC (May 2007). "Visualization of the Herpes Simplex Virus Portal in situ by Cryo-electron Tomography". Virology. 361 (2): 426–34. doi:10.1016/j.virol.2006.10.047. PMC 1930166. PMID 17188319.

[pmid15507654-18] Trus BL, Cheng N, Newcomb WW, Homa FL, Brown JC, Steven AC (November 2004). "Structure and Polymorphism of the UL6 Portal Protein of Herpes Simplex Virus Type 1". Journal of Virology. 78 (22): 12668–71. doi:10.1128/JVI.78.22.12668-12671.2004. PMC 525097. PMID 15507654.

[Nellissery_2007-19] Nellissery JK, Szczepaniak R, Lamberti C, Weller SK (2007-06-20). "A Putative Leucine Zipper within the Herpes Simplex Virus Type 1 UL6 Protein Is Required for Portal Ring Formation". Journal Virology. 81 (17): 8868–77. doi:10.1128/JVI.00739-07. PMC 1951442. PMID 17581990.

[pmid17540405-20] Newcomb WW, Booy FP, Brown JC (2007). "Uncoating the Herpes Simplex Virus Genome". J. Mol. Biol. 370 (4): 633–42. doi:10.1016/j.jmb.2007.05.023. PMC 1975772. PMID 17540405.

[21] Abbas et al (2009) Cellular and Molecular Immunology, Elsevier Inc.

[PMID_17005685-22] Adang LA, Parsons CH, Kedes DH (2006). "Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection". J. Virol. 80 (20): 10073–82. doi:10.1128/JVI.01156-06. PMC 1617294. PMID 17005685.

[pmid12083325-23] Matis J, Kúdelová M (2001). "Early shutoff of host protein synthesis in cells infected with herpes simplex viruses". Acta Virol. 45 (5–6): 269–77. doi:10.2217/fvl.11.24. PMID 12083325.

[pmid16940547-24] Taddeo B, Roizman B (2006). "The Virion Host Shutoff Protein (UL41) of Herpes Simplex Virus 1 Is an Endoribonuclease with a Substrate Specificity Similar to That of RNase A". J. Virol. 80 (18): 9341–5. doi:10.1128/JVI.01008-06. PMC 1563938. PMID 16940547.

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v t e Sexually transmitted infection (STI) (primarily A50–A64, 090–099)

Bacterial	Chancroid (Haemophilus ducreyi) Chlamydia/Lymphogranuloma venereum (Chlamydia trachomatis) Donovanosis or Granuloma Inguinale (Klebsiella granulomatis) Gonorrhea (Neisseria gonorrhoeae) Mycoplasma hominis infection (Mycoplasma hominis) Syphilis (Treponema pallidum) Ureaplasma infection (Ureaplasma urealyticum)

Protozoal	Trichomoniasis (Trichomonas vaginalis)

Parasitic	Crab louse/crabs Scabies

Viral	AIDS (HIV-1/HIV-2) Cervical cancer, vulvar cancer & Genital warts (condyloma), Penile cancer, Anal cancer (Human papillomavirus (HPV)) Hepatitis B (Hepatitis B virus) Herpes simplex *(HSV1/HSV2)* Molluscum contagiosum (MCV)

General inflammation	female Cervicitis Pelvic inflammatory disease (PID) male Epididymitis Prostatitis either Proctitis Urethritis/Non-gonococcal urethritis (NGU)

匿名

検索

案内

HHV-2