Chapter 26 : Herpes Simplex Viruses and Varicella Zoster Virus

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Herpes Simplex Viruses and Varicella Zoster Virus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819156/9781555819149.ch26-1.gif /docserver/preview/fulltext/10.1128/9781555819156/9781555819149.ch26-2.gif


The herpesviruses are classified in the family based on the characteristic large linear double-stranded DNA genome packaged within an enveloped icosahedral capsid. Members of this family have been identified in almost all animal species, and the specific herpesviruses are usually restricted to a single species. Nine human herpesviruses have been described: HSV-1, HSV-2, varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (CMV), human herpesvirus 6A (HHV-6A), human herpesvirus 6B (HHV-6B), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8). All these viruses are structurally similar and encode a large number of biosynthetic enzymes involved in the synthesis of viral DNA as well as structure proteins that compose the capsid and tegument, as well as envelope glycoproteins that are required for infection.

Citation: James S, Prichard M. 2016. Herpes Simplex Viruses and Varicella Zoster Virus, p 363-371. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch26
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Antiviral therapies for HSV and VZV. (A) Therapies for the treatment of HSV and VZV are shown with prodrugs shown in parentheses. The pyrophosphate analog foscarnet is approved for resistant therapies. Cidofovir is also active against resistant isolates, but it has not been approved for that indication. (B) Acyclovir, the therapy of choice, is initially phosphorylated exclusively by the TK enzymes encoded by HSV-1, HSV-2, and VZV to the level of the monophosphate (ACV-MP). Cellular kinases further phosphorylate the drug to the active triphosphate metabolite (ACV-TP) that inhibits the viral DNA polymerase. Most drug-resistant viruses contain mutations in the TK that impair its ability to phosphorylate the drug and limits the concentration of the active metabolite. Neither foscarnet nor cidofovir require the TK such that both drugs are active against drug-resistant isolates of the virus.

Citation: James S, Prichard M. 2016. Herpes Simplex Viruses and Varicella Zoster Virus, p 363-371. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch26
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Algorithm for the diagnosis of HSV and VZV infections. If no lesions are present and time is not a critical factor, serological testing can identify patients infected with HSV or VZV. Further testing for HSV shown in the box can type the infection as being HSV-1 or HSV-2. If lesions are present, swab specimens can be cultured, and infected cultures can be further tested by fluorescent antibody to identify the infection as being HSV or VZV. For high-risk or time-critical specimens (or as an alternative to viral culture), PCR of specimens can be used to identify DNA from HSV or VZV. Many standard assays also distinguish between HSV-1 and HSV-2 at this stage.

Citation: James S, Prichard M. 2016. Herpes Simplex Viruses and Varicella Zoster Virus, p 363-371. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch26
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Whitley RJ, Roizman B, Knipe D, . 2007. Herpes simplex viruses, p 2501 2601. In Knipe DM, Howley PM, Griffin D, Lamb R, Martin M, Straus SE (eds), Fields Virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
2. Ward S, Weller SK, . 2011. HSV-1 DNA replication, p 89 112. In Weller SK (ed), Alphaherpesviruses: Molecular Virology. Caister Academic Press, Norfolk, UK.
3. Weller SK, Coen DM . 2012. Herpes simplex viruses: mechanisms of DNA replication. Cold Spring Harb Perspect Biol 4 : a013011.[PubMed]
4. Lehman IR, Boehmer PE . 1999. Replication of herpes simplex virus DNA. J Biol Chem 274 : 28059 28062.[PubMed]
5. Smith JS, Robinson NJ . 2002. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis 186( Suppl 1) : S3 S28.[PubMed]
6. Nahmias AJ, Lee FK, Beckman-Nahmias S . 1990. Sero-epidemiological and -sociological patterns of herpes simplex virus infection in the world. Scand J Infect Dis Suppl 69 : 19 36.[PubMed]
7. Tunbäck P, Bergström T, Andersson AS, Nordin P, Krantz I, Löwhagen GB . 2003. Prevalence of herpes simplex virus antibodies in childhood and adolescence: a cross-sectional study. Scand J Infect Dis 35 : 498 502.[PubMed]
8. Corey L, Huang ML, Selke S, Wald A . 2005. Differentiation of herpes simplex virus types 1 and 2 in clinical samples by a real-time taqman PCR assay. J Med Virol 76 : 350 355.[PubMed]
9. Bernstein DI, Bellamy AR, Hook EW III, Levin MJ, Wald A, Ewell MG, Wolff PA, Deal CD, Heineman TC, Dubin G, Belshe RB . 2013. Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women. Clin Infect Dis 56 : 344 351.[PubMed]
10. Roberts CM, Pfister JR, Spear SJ . 2003. Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis 30 : 797 800.[PubMed]
11. Corey L, Wald A, Celum CL, Quinn TC . 2004. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Acquir Immune Defic Syndr 35 : 435 445.[PubMed]
12. Fleming DT, McQuillan GM, Johnson RE, Nahmias AJ, Aral SO, Lee FK, St Louis ME . 1997. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 337 : 1105 1111.[PubMed]
13. Xu F, Sternberg MR, Kottiri BJ, McQuillan GM, Lee FK, Nahmias AJ, Berman SM, Markowitz LE . 2006. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA 296 : 964 973.[PubMed]
14. Bradley H, Markowitz LE, Gibson T, McQuillan GM. 2013. Seroprevalence of herpes simplex virus types 1 and 2—United States, 1999–2010. J Infect Dis 209 : 325 333.[PubMed]
15. Kelley PW, Petruccelli BP, Stehr-Green P, Erickson RL, Mason CJ . 1991. The susceptibility of young adult Americans to vaccine-preventable infections. A national serosurvey of US Army recruits. JAMA 266 : 2724 2729.[PubMed]
16. Weinberg JM . 2007. Herpes zoster: epidemiology, natural history, and common complications. J Am Acad Dermatol 57( Suppl) : S130 S135.[PubMed]
17. Baxter R, Tran TN, Ray P, Lewis E, Fireman B, Black S, Shinefield HR, Coplan PM, Saddier P . 2014. Impact of vaccination on the epidemiology of varicella: 1995–2009. Pediatrics 134 : 24 30.[PubMed]
18. Kimberlin DW . 2007. Management of HSV encephalitis in adults and neonates: diagnosis, prognosis and treatment. Herpes 14 : 11 16.[PubMed]
19. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L . 2003. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 289 : 203 209.[PubMed]
20. Kropp RY, Wong T, Cormier L, Ringrose A, Burton S, Embree JE, Steben M . 2006. Neonatal herpes simplex virus infections in Canada: results of a 3-year national prospective study. Pediatrics 117 : 1955 1962.[PubMed]
21. Jones CA, Raynes-Greenow C, Issacs D . 2014. Population-based surveillance of neonatal HSV infection in Australia (1997–2011). Clin Infect Dis 59 : 525 531.
22. Andrei G, Snoeck R . 2013. Advances in the treatment of varicella-zoster virus infections. Adv Pharmacol 67 : 107 168.[PubMed]
23. Vere Hodge RA, Field HJ . 2013. Antiviral agents for herpes simplex virus. Adv Pharmacol 67 : 1 38.[PubMed]
24. James SH, Prichard MN . 2014. Current and future therapies for herpes simplex virus infections: mechanism of action and drug resistance. Curr Opin Virol 8 : 54 61.[PubMed]
25. Elion GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ . 1977. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci USA 74 : 5716 5720.[PubMed]
26. Vere Hodge RA, Sutton D, Boyd MR, Harnden MR, Jarvest RL . 1989. Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine; penciclovir]. Antimicrob Agents Chemother 33 : 1765 1773.[PubMed]
27. Öberg B . 1989. Antiviral effects of phosphonoformate (PFA, foscarnet sodium). Pharmacol Ther 40 : 213 285.[PubMed]
28. De Clercq E, Holý A . 2005. Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nat Rev Drug Discov 4 : 928 940.[PubMed]
29. Cihlar T, Chen MS . 1996. Identification of enzymes catalyzing two-step phosphorylation of cidofovir and the effect of cytomegalovirus infection on their activities in host cells. Mol Pharmacol 50 : 1502 1510.[PubMed]
30. Shapiro ED, Vazquez M, Esposito D, Holabird N, Steinberg SP, Dziura J, LaRussa PS, Gershon AA . 2011. Effectiveness of 2 doses of varicella vaccine in children. J Infect Dis 203 : 312 315.[PubMed]
31. Gnann JW Jr . 2008. Vaccination to prevent herpes zoster in older adults. J Pain 9( 1 Suppl 1) : S31 S36.[PubMed]
32. Dworkin RH, Johnson RW, Breuer J, Gnann JW, Levin MJ, Backonja M, Betts RF, Gershon AA, Haanpaa ML, McKendrick MW, Nurmikko TJ, Oaklander AL, Oxman MN, Pavan-Langston D, Petersen KL, Rowbotham MC, Schmader KE, Stacey BR, Tyring SK, van Wijck AJ, Wallace MS, Wassilew SW, Whitley RJ . 2007. Recommendations for the management of herpes zoster. Clin Infect Dis 44( Suppl 1) : S1 S26.[PubMed]
33. Shepp DH, Dandliker PS, Meyers JD . 1986. Treatment of varicella-zoster virus infection in severely immunocompromised patients. A randomized comparison of acyclovir and vidarabine. N Engl J Med 314 : 208 212.[PubMed]
34. Bryan CJ, Prichard MN, Daily S, Jefferson G, Hartline C, Cassady KA, Hilliard L, Shimamura M . 2008. Acyclovir-resistant chronic verrucous vaccine strain varicella in a patient with neuroblastoma. Pediatr Infect Dis J 27 : 946 948.[PubMed]
35. Lakeman FD, Whitley RJ National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group . 1995. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. J Infect Dis 171 : 857 863.[PubMed]
36. Crist GA, Langer JM, Woods GL, Procter M, Hillyard DR . 2004. Evaluation of the ELVIS plate method for the detection and typing of herpes simplex virus in clinical specimens. Diagn Microbiol Infect Dis 49 : 173 177.[PubMed]
37. Wald A, Ashley-Morrow R . 2002. Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection. Clin Infect Dis 35( Suppl 2) : S173 S182.[PubMed]
38. Whitley RJ, Lakeman F . 1995. Herpes simplex virus infections of the central nervous system: therapeutic and diagnostic considerations. Clin Infect Dis 20 : 414 420.[PubMed]
39. Kimberlin DW, Lakeman FD, Arvin AM, Prober CG, Corey L, Powell DA, Burchett SK, Jacobs RF, Starr SE, Whitley RJ National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group . 1996. Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. J Infect Dis 174 : 1162 1167.[PubMed]
40. Wald A, Huang ML, Carrell D, Selke S, Corey L . 2003. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis 188 : 1345 1351.[PubMed]
41. Thompson PP, Kowalski RP . 2011. A 13-year retrospective review of polymerase chain reaction testing for infectious agents from ocular samples. Ophthalmology 118 : 1449 1453.[PubMed]
42. Van Der Pol B, Warren T, Taylor SN, Martens M, Jerome KR, Mena L, Lebed J, Ginde S, Fine P, Hook EW 3rd . 2012. Type-specific identification of anogenital herpes simplex virus infections by use of a commercially available nucleic acid amplification test. J Clin Microbiol 50 : 3466 3471.[PubMed]
43. Binnicker MJ, Espy MJ, Irish CL . 2014. Rapid and direct detection of herpes simplex virus in cerebrospinal fluid by use of a commercial real-time PCR assay. J Clin Microbiol 52 : 4361 4362.[PubMed]
44. Fan F, Stiles J, Mikhlina A, Lu X, Babady NE, Tang YW . 2014. Clinical validation of the Lyra direct HSV 1+2/VZV assay for simultaneous detection and differentiation of three herpesviruses in cutaneous and mucocutaneous lesions. J Clin Microbiol 52 : 3799 3801.[PubMed]
45. Heaton PR, Espy MJ, Binnicker MJ . 2015. Evaluation of 2 multiplex real-time PCR assays for the detection of HSV-1/2 and Varicella zoster virus directly from clinical samples. Diagn Microbiol Infect Dis 81 : 169 170.[PubMed]
46. Hodinka RL . 2013. Point: is the era of viral culture over in the clinical microbiology laboratory? J Clin Microbiol 51 : 2 4.[PubMed]
47. Coffin SE, Hodinka RL . 1995. Utility of direct immunofluorescence and virus culture for detection of varicella-zoster virus in skin lesions. J Clin Microbiol 33 : 2792 2795.[PubMed]
48. Sauerbrei A, Wutzler P . 2006. Serological detection of varicella-zoster virus-specific immunoglobulin G by an enzyme-linked immunosorbent assay using glycoprotein antigen. J Clin Microbiol 44 : 3094 3097.[PubMed]
49. Kalpoe JS, Kroes AC, Verkerk S, Claas EC, Barge RM, Beersma MF . 2006. Clinical relevance of quantitative varicella-zoster virus (VZV) DNA detection in plasma after stem cell transplantation. Bone Marrow Transplant 38 : 41 46.[PubMed]
50. Pevenstein SR, Williams RK, McChesney D, Mont EK, Smialek JE, Straus SE . 1999. Quantitation of latent varicella-zoster virus and herpes simplex virus genomes in human trigeminal ganglia. J Virol 73 : 10514 10518.[PubMed]
51. Espy MJ, Teo R, Ross TK, Svien KA, Wold AD, Uhl JR, Smith TF . 2000. Diagnosis of varicella-zoster virus infections in the clinical laboratory by LightCycler PCR. J Clin Microbiol 38 : 3187 3189.[PubMed]
52. Kalpoe JS, van Dehn CE, Bollemeijer JG, Vaessen N, Claas EC, Barge RM, Willemze R, Kroes AC, Beersma MF . 2005. Varicella zoster virus (VZV)-related progressive outer retinal necrosis (PORN) after allogeneic stem cell transplantation. Bone Marrow Transplant 36 : 467 469.[PubMed]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error