Current Thinking on Genital Herpes

Annika M. Hofstetter; Susan L. Rosenthal; Lawrence R. Stanberry

Disclosures

Curr Opin Infect Dis. 2014;27(1):75-83. 

In This Article

Herpes Simplex Virus Reactivation

Some of the most important recent advancements in our understanding of genital herpes pathogenesis relate to HSV reactivation following latency. Simultaneous reactivation at multiple ganglia leads to anterograde HSV transport in neuronal axons to epidermal cells where viral replication occurs and spreads to adjacent cells. This may result in shedding, with or without characteristic lesions, at multiple anatomical sites within the genital tract.[40,41] Recent studies using repeat genital sampling and spatial mathematical modelling have demonstrated that reactivations are brief (i.e. <12 h) and occur frequently.[41,42] Greater efficiency of viral reactivation and replication in the genital tract has been detected for HSV-2 than for HSV-1.[43] This may reflect a distinct predilection for sacral ganglia (HSV-2) compared with trigeminal ganglia (HSV-1) that likely evolved as these two closely related viruses diverged from a common ancestor.[44,45] Unique latency-associated transcript (LAT) regions of the two viruses may modulate these processes,[46] including the site-specific reactivation profile.[47,48]

Recurrence

HSV recurrence, defined as HSV reactivation resulting in symptomatic presentation, occurs in approximately 57 and 89% of individuals with a history of primary genital HSV-1 or HSV-2 infection, respectively.[49,50] Recurrence is typically less severe and of shorter duration than primary infection.[51] Individuals with genital HSV-1 infection have a median of 1.3 recurrences per year,[49] whereas those with genital HSV-2 infection have a median of four recurrences per year.[50] The higher recurrence rate among those with HSV-2 vs. HSV-1 infection again may reflect site-specificity, as described above. Other factors such as male sex and severity of primary infection are also associated with greater recurrence frequency.[50]

Asymptomatic Viral Shedding

Although it was originally postulated that HSV shedding was rare given that symptomatic recurrences are infrequent, numerous studies now refute this idea. The use of PCR amplification, as opposed to less sensitive viral culture,[52] and at least daily sampling have enabled detection of asymptomatic shedding in the genital tract of 80–90% of HSV-2 seropositive individuals on approximately 20% of days.[42,53–59] Asymptomatic genital HSV-1 shedding has also been described in patients with prior symptomatic genital HSV-1 infection.[54] Shedding episodes are typically brief, may overlap with subsequent reactivations and continue to occur over time, although with decreasing frequency.[60–62] The discovery that so many asymptomatic patients experience silent reactivation and frequent shedding episodes that persist over time has significant public health implications. Indeed, data indicate that most HSV transmission occurs while patients are asymptomatic, even though there is a higher risk of transmission when they possess active lesions and a greater viral load.[63,64]

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