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Chapter 19 : Herpes Simplex Viruses
Authors:
Richard J. Whitley,
Bernard Roizman
Content Type: Reference
Publication Year:
2009
Category: Viruses and Viral Pathogenesis
Book DOI:
10.1128/9781555815981
Chapter DOI:
10.1128/9781555815981.ch19
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Herpes Simplex Viruses, Page 1 of 2
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Abstract:
Herpes simplex virus (HSV) infections of humans have been documented since the advent of writing. The spectrum of disease was expanded to include primary and recurrent infections of mucous membranes (gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, HSV encephalitis, Kaposi's varicella-like eruption, and an association with erythema multiforme. Cumulative experience suggests that factors associated with pregnancy may place both the mother and fetus at increased risk for severe infection, possibly because of altered cell-mediated immunity. The major risk to the fetus is with primary or initial genital HSV infection of the mother. PCR evaluation of cerebrospinal fluid can be utilized to monitor therapeutic outcome in patients with herpes simplex encephalitis. The use of HSV for gene therapy heralds a new era of herpes biology, the conversion of a hazardous foe into a user-friendly surgical tool. Asymptomatic shedding of virus can continue despite clinically effective suppression with acyclovir, so the possibility of person-to-person transmission persists. Newborns with HSV infections can be classified as having disease that is localized to the skin, eyes, and mouth; affects the central nervous system (CNS); or is disseminated. Drug resistance was considered rare and resistant isolates were thought to be less pathogenic until a series of acyclovir-resistant HSV isolates from patients with AIDS were characterized. The risk of nephrotoxicity can be minimized by administering acyclovir by slow infusion and ensuring adequate hydration.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
Figures
Herpes Simplex Viruses
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Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig01
FIGURE 1
Schematic representation of the replication of HSVs in susceptible cells. 1, The virus initiates infection by fusion of the viral envelope with the plasma membrane following attachment to the cell surface. 2, Fusion of the membranes releases two proteins from the virion. VHS shuts off protein synthesis (broken RNA in open polyribosomes). α-TIF (the α gene trans-inducing factor) is transported to the nucleus. 3, The capsid is transported to the nuclear pore, where viral DNA is released into the nucleus and immediately circularizes. 4, The transcription of α genes by cellular enzymes is induced by α-TIF. 5, The five α mRNAs are transported into the cytoplasm and translated (filled polyribosome); the proteins are transported into the nucleus. 6, A new round of transcription results in the synthesis of β proteins. 7, At this stage in the infection, the chromatin (c) is degraded and displaced toward the nuclear membrane, whereas the nucleoli (round hatched structures) become disaggregated. 8, Viral DNA is replicated by a rolling-circle mechanism which yields head-to-tail concatemers of unit length viral DNA. 9, A new round of transcription/translation yields the γ proteins, consisting primarily of structural proteins of the virus. 10, The capsid proteins form empty capsids. 11, Unit length viral DNA is cleaved from concatemers and packaged into the preformed capsids. 12, Capsids containing viral DNA acquire a new protein. 13, Viral glycoproteins and tegument proteins accumulate and form patches in cellular membranes. The capsids containing DNA and the additional protein attach to the underside of the membrane patches containing viral proteins and are enveloped. 14, The enveloped proteins accumulate in the endoplasmic reticulum and are transported into the extracellular space. BR, Bernard Roizman. (Reprinted from reference
118
with permission.)
10.1128/9781555815981/f0411-01_thmb.gif
10.1128/9781555815981/f0411-01.gif
FIGURE 1
Schematic representation of the replication of HSVs in susceptible cells. 1, The virus initiates infection by fusion of the viral envelope with the plasma membrane following attachment to the cell surface. 2, Fusion of the membranes releases two proteins from the virion. VHS shuts off protein synthesis (broken RNA in open polyribosomes). α-TIF (the α gene trans-inducing factor) is transported to the nucleus. 3, The capsid is transported to the nuclear pore, where viral DNA is released into the nucleus and immediately circularizes. 4, The transcription of α genes by cellular enzymes is induced by α-TIF. 5, The five α mRNAs are transported into the cytoplasm and translated (filled polyribosome); the proteins are transported into the nucleus. 6, A new round of transcription results in the synthesis of β proteins. 7, At this stage in the infection, the chromatin (c) is degraded and displaced toward the nuclear membrane, whereas the nucleoli (round hatched structures) become disaggregated. 8, Viral DNA is replicated by a rolling-circle mechanism which yields head-to-tail concatemers of unit length viral DNA. 9, A new round of transcription/translation yields the γ proteins, consisting primarily of structural proteins of the virus. 10, The capsid proteins form empty capsids. 11, Unit length viral DNA is cleaved from concatemers and packaged into the preformed capsids. 12, Capsids containing viral DNA acquire a new protein. 13, Viral glycoproteins and tegument proteins accumulate and form patches in cellular membranes. The capsids containing DNA and the additional protein attach to the underside of the membrane patches containing viral proteins and are enveloped. 14, The enveloped proteins accumulate in the endoplasmic reticulum and are transported into the extracellular space. BR, Bernard Roizman. (Reprinted from reference 118 with permission.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig02
FIGURE 2
Seroprevalence of HSV-1 and HSV-2 by age.
10.1128/9781555815981/f0414-01_thmb.gif
10.1128/9781555815981/f0414-01.gif
FIGURE 2
Seroprevalence of HSV-1 and HSV-2 by age.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig03
FIGURE 3
Seroprevalence of HSV-1 and HSV-2 by selected country. T2, HSV-2 antibodies; T1, HSV-1 antibodies. (Reprinted from reference
97
with permission.)
10.1128/9781555815981/f0415-01_thmb.gif
10.1128/9781555815981/f0415-01.gif
FIGURE 3
Seroprevalence of HSV-1 and HSV-2 by selected country. T2, HSV-2 antibodies; T1, HSV-1 antibodies. (Reprinted from reference 97 with permission.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig04
FIGURE 4
Seroprevalence of HSV-2 as a function of the number of sexual partners. Numbers above bars indicate percentages of population. (Reprinted from reference
97
with permission.)
10.1128/9781555815981/f0416-01_thmb.gif
10.1128/9781555815981/f0416-01.gif
FIGURE 4
Seroprevalence of HSV-2 as a function of the number of sexual partners. Numbers above bars indicate percentages of population. (Reprinted from reference 97 with permission.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig05
FIGURE 5
Histopathology of HSV infection.
10.1128/9781555815981/f0417-02_thmb.gif
10.1128/9781555815981/f0417-02.gif
FIGURE 5
Histopathology of HSV infection.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig06
FIGURE 6
Schematic diagram of primary HSV infection. (Reprinted from reference
93a
with permission of Elsevier.)
10.1128/9781555815981/f0417-01_thmb.gif
10.1128/9781555815981/f0417-01.gif
FIGURE 6
Schematic diagram of primary HSV infection. (Reprinted from reference 93a with permission of Elsevier.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig07
FIGURE 7
Schematic diagram of latency and reactivation. (Reprinted from reference
93a
with permission of Elsevier.)
10.1128/9781555815981/f0418-01_thmb.gif
10.1128/9781555815981/f0418-01.gif
FIGURE 7
Schematic diagram of latency and reactivation. (Reprinted from reference 93a with permission of Elsevier.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig08
FIGURE 8
Sites of HSV infection and disease.
10.1128/9781555815981/f0418-02_thmb.gif
10.1128/9781555815981/f0418-02.gif
FIGURE 8
Sites of HSV infection and disease.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig09
FIGURE 9
Herpes simplex gingivostomatitis.
10.1128/9781555815981/f0420-01_thmb.gif
10.1128/9781555815981/f0420-01.gif
FIGURE 9
Herpes simplex gingivostomatitis.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig10
FIGURE 10
Recurrent herpes simplex labialis.
10.1128/9781555815981/f0420-02_thmb.gif
10.1128/9781555815981/f0420-02.gif
FIGURE 10
Recurrent herpes simplex labialis.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig11
FIGURE 11
Genital HSV infection (female). (Reprinted from reference
93b
with permission of Elsevier.)
10.1128/9781555815981/f0421-01_thmb.gif
10.1128/9781555815981/f0421-01.gif
FIGURE 11
Genital HSV infection (female). (Reprinted from reference 93b with permission of Elsevier.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig12
FIGURE 12
Genital HSV infection (male).
10.1128/9781555815981/f0421-02_thmb.gif
10.1128/9781555815981/f0421-02.gif
FIGURE 12
Genital HSV infection (male).
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig13
FIGURE 13
Vesicular rash of neonatal HSV infection.
10.1128/9781555815981/f0423-01_thmb.gif
10.1128/9781555815981/f0423-01.gif
FIGURE 13
Vesicular rash of neonatal HSV infection.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig14
FIGURE 14
Cutaneous dissemination of HSV infection in an immunosuppressed host.
10.1128/9781555815981/f0424-01_thmb.gif
10.1128/9781555815981/f0424-01.gif
FIGURE 14
Cutaneous dissemination of HSV infection in an immunosuppressed host.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig15
FIGURE 15
Coronal sections of brain from a patient with herpes simplex encephalitis.
10.1128/9781555815981/f0425-01_thmb.gif
10.1128/9781555815981/f0425-01.gif
FIGURE 15
Coronal sections of brain from a patient with herpes simplex encephalitis.
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig16
FIGURE 16
Clearance of virus from patients with primary genital HSV infection, according to the route of drug delivery. Δ, intravenous acyclovir; ■, oral acyclovir; ○, topical acyclovir. (Reprinted from reference
33
with permission.)
10.1128/9781555815981/f0428-01_thmb.gif
10.1128/9781555815981/f0428-01.gif
FIGURE 16
Clearance of virus from patients with primary genital HSV infection, according to the route of drug delivery. Δ, intravenous acyclovir; ■, oral acyclovir; ○, topical acyclovir. (Reprinted from reference 33 with permission.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig17
FIGURE 17
Acyclovir therapy of mucocutaneous HSV infections in immunocompromised patients, according to the clearance of virus (A) and the extent of healing (B). (Reprinted from reference
93a
with permission of Elsevier.)
10.1128/9781555815981/f0430-01_thmb.gif
10.1128/9781555815981/f0430-01.gif
FIGURE 17
Acyclovir therapy of mucocutaneous HSV infections in immunocompromised patients, according to the clearance of virus (A) and the extent of healing (B). (Reprinted from reference 93a with permission of Elsevier.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19fig18
FIGURE 18
Comparison of survival in patients with biopsy-proven herpes simplex encephalitis treated with vidarabine (ARA-A) or acyclovir (ACV). (Reprinted from reference
93a
with permission of Elsevier.)
10.1128/9781555815981/f0430-02_thmb.gif
10.1128/9781555815981/f0430-02.gif
FIGURE 18
Comparison of survival in patients with biopsy-proven herpes simplex encephalitis treated with vidarabine (ARA-A) or acyclovir (ACV). (Reprinted from reference 93a with permission of Elsevier.)
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
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Tables
Herpes Simplex Viruses
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Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19tab01
TABLE 1
Indications for acyclovir therapy
TABLE 1
Indications for acyclovir therapy
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19
/content/10.1128/9781555815981.ch19.ch19tab02
TABLE 2
Investigational uses of acyclovir
TABLE 2
Investigational uses of acyclovir
Citation:
Whitley R, Roizman B.
2009.
Herpes Simplex Viruses,
p 409-436.
In
Richman D, Whitley R, Hayden F (ed),
Clinical Virology, Third Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555815981.ch19