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Changing Viral Epidemiology: the present‐ equilibrium viruses & interventions
• Herpes simplex viruses5,6 are evolutionarily ancient and ubiquitous. In the past 20 years, there has been increasing recognition of a worldwide pandemic of HSV‐2 infection. Moreover, HSV‐2 prevalence has increased despite fairly widespread use of antiviral drugs for HSV.
• In January 2015, WHO estimated that 417 million people aged 15‐49 years have HSV‐2 infection, which causes genital herpes. Taken together, the estimates reveal that over half a billion people between the ages of 15‐49 years have genital infection caused by either HSV‐1 or HSV‐2.
• An estimated 3.7 billion people under age 50 (67%) have HSV‐1 infection globally.
• An estimated 417 million people aged 15‐49 (11%) worldwide have HSV‐2 infection.
HSV Pathogenesis/Equilibrium
• HSV DNA in sensory ganglia neurons directs synthesis of mRNA molecules that encode proteins required for HSV DNA replication and assembly of daughter virions. Viral components move anterograde toward epithelia, and infectious virus is released without neuronal death
• HSV DNA can trigger responses via TLR9 and Innate immunity defects have emerged as correlates of severe HSV infections
The success of HSV‐1 and HSV‐2 stems from latency within long lived neurons and
• IFN evasion functions mediated by several HSV‐encoded proteins that inhibit frequent mucocutaneous shedding. The generally mild medical consequences of HSV
Interferon stimulated gene expression
infection reflect a functional equilibrium between host and microbe in most
immunocompetent persons5,6.
• In the periphery, HSV‐2‐specific CD8 Tcells are attracted to GH lesions, where the
infiltration of local cytotoxic T cells correlates with viral clearance
• Unbiased library screens and clonal dominance studies indicate that tegument‐
specific CD8 T cells may be somewhat immunodominant
• Antibodies are functionally relevant in the prevention of neonatal transmission of HSV‐1 or HSV‐2 in the setting of chronic infection, a mature IgG response that can cross the placenta, and recurrent cervicovaginal shedding at delivery.
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