Herpes simplex virus infection

Herpes simplex virus type 1 (HSV-1) more commonly causes herpes labialis; however, it is also an increasing cause of initial episodes of genital herpes.[14]Ryder N, Jin F, McNulty AM, et al. Increasing role of herpes simplex virus type 1 in first-episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992-2006. Sex Transm Infect. 2009 Mar 8;85(6):416-9. http://www.ncbi.nlm.nih.gov/pubmed/19273479?tool=bestpractice.com [15]Bernstein DI, Bellamy AR, Hook EW 3rd, et al. Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women. Clin Infect Dis. 2012 Oct 19;56(3):344-51. https://www.doi.org/10.1093/cid/cis891 http://www.ncbi.nlm.nih.gov/pubmed/23087395?tool=bestpractice.com [16]Roberts CM, Pfister JR, Spear SJ. Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis. 2003 Oct;30(10):797-800. http://www.ncbi.nlm.nih.gov/pubmed/14520181?tool=bestpractice.com  HSV-1 is also associated with HSV encephalitis. HSV type 2 (HSV-2) causes genital herpes.

HSV-1 and HSV-2 are members of the Herpesviridae family and are related to varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6, -7, and -8. HSV-1 and HSV-2 are large, enveloped, double-stranded DNA viruses. The genome encodes 84 proteins, with type-specific differences in several proteins, including proteins involved in host immunity. The viruses are 50% homologous at the genomic level.

HSV can exist in both a latent and a lytic state. During latency, infectious virions are not produced. Latently infected cells persist for the life cycle of the host, causing chronic infection. Lytic infection is characterized by viral replication and transport of the virus to the skin, with infection of skin and mucosal surfaces.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are acquired at mucosal surfaces or at breaks in the skin.[17]Cunningham A, Diefenbach RJ, Miranda-Saksena M, et al. The cycle of human herpes simplex virus infection: viral transport and immune control. J Infect Dis. 2006 Sep 15;194(suppl 1):S11-8. http://www.ncbi.nlm.nih.gov/pubmed/16921466?tool=bestpractice.com Acquisition of the virus is often asymptomatic. The virus initially replicates in the epidermis, then infects sensory or autonomic nerve endings and travels by retrograde axonal transport to sensory ganglia. It then enters a latent state, which allows the virus to evade the immune system and cause lifelong infection.

Periodic reactivation of the virus produces lytic replication when the virus travels by anterograde transport down axons to the mucosal or cutaneous surface. Reactivation may lead to asymptomatic shedding of the virus or to a range of symptoms from neuropathic tingling and burning to recurrent ulceration. Transmission of the virus may occur during asymptomatic or symptomatic viral reactivation.[18]Mertz GJ, Benedetti J, Ashley R, et al. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992 Feb 1;116(3):197-202. http://www.ncbi.nlm.nih.gov/pubmed/1309413?tool=bestpractice.com  HSV infection is accompanied by CD4+ and CD8+ T-cell response as well as antibody production. CD8+ T cells are found both at the ganglia and at peripheral mucosal sites and restrict viral replication.

Herpesvirus classification[1]Burrell CJ, Howard CR, Murphy FA. Fenner and White's Medical Virology. 5th ed. New York, NY. Elsevier; 2017.

Human herpesvirus (HHV) classification:

• Alphaherpesvirinae

  • HHV-1: HSV-1: oral and/or genital herpes

  • HHV-2: HSV-2: oral and/or genital herpes (mainly genital)

  • HHV-3: varicella-zoster virus (VZV): chickenpox and shingles

• Betaherpesvirinae

  • HHV-5: Cytomegalovirus: infectious mononucleosis-like syndrome, retinitis

  • HHV-6, HHV-7: roseolovirus: sixth disease (roseola infantum or exanthema subitum)

• Gammaherpesvirinae

  • HHV-4: Epstein-Barr virus, lymphocryptovirus: infectious mononucleosis, Burkitt lymphoma, central nervous system lymphoma in AIDS, post-transplant lymphoproliferative syndrome, nasopharyngeal carcinoma

  • HHV-8: Kaposi sarcoma-associated herpesvirus: Kaposi sarcoma, primary effusion lymphoma, Castleman disease.

Zoonotic herpesvirus infections:

• MHV-1: B virus, Macacine herpesvirus 1 (previously known as Cercopithecine herpesvirus 1): ascending paralysis and encephalitis (rare, acquired from infected macaque monkeys).