Summary of Latent Infection

Acute infection is typically initiated in the mucosal epithelium, and then HSV-1 establishes latency in sensory neurons located in trigeminal ganglia (TG) or sacral dorsal root ganglia. Despite a vigorous immune response during acute infection, latency is established. As many as 20-30% of sensory neurons are latently infected (reviewed in Tones, 1998, 2003). As a consequence of primary infection, HSV-1 genomic DNA is also present in the central nervous system (CNS) of a significant proportion of the adult human population (Fraser et al., 1981). 

The latency associated transcript (LAT) is abundantly transcribed in latendy infected neurons (reviewed in Jones, 1998, 2003). Mice, rabbits, or humans latently infected with HSV-1 express LAT. In productively infected cells or latently infected rabbits, an 8.3-Kb transcript is expressed that has the same sense as LAT. Splicing of the 8.3-Kb transcript yields an abundant 2-Kb LAT and an unstable 6.3-Kb LAT. The majority of LAT is not capped, is poly A-, appears to be circular, and is designated as a stable intron. In small animal models, LAT is important but not required for the latency-reactivation cycle (reviewed in Tones, 1998, 2003). The first 1.5 Kb of LAT coding sequences are important for reactivation from latency. It is not clear vriether LAT encodes a protein or is a regulatory RNA. 

LAT interferes with apoptosis in transiently transfected cells and in TG of infected rabbits or mice (Jones, 2003). Inhibiting apoptosis may be the most important function of LAT because two anti-apoptosis genes, the bovine herpesvirus 1 (BHV-1) LAT homologue (Mott et al., 2003 Pemg et al., 2002) and the baculovirus lAP gene (Jin et al., 2005), can restore levels of spontaneous reactivation to a LAT null mutant. 

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