Scientific Publications by FDA Staff

J Virol 2007 Feb;81(4):1872-8

HSV-2 Establishes Latent Infection In a Different Population of Ganglionic Neurons than HSV-1: Role of LAT.

Margolis TP, Imai Y, Yang L, Vallas V, Krause PR

HSV-1 and HSV-2 cause very similar acute infections, but differ in their ability to reactivate from trigeminal and dorsal root ganglia. To investigate differences in patterns of viral infection, we co-labeled murine sensory ganglia for evidence of HSV infection and for the sensory neuron markers A5 or KH10. During acute infection, 7-10% of HSV-1 or HSV-2 antigen-positive neurons were A5-positive, and 13-16% were KH10-positive, suggesting that both viruses reach each type of neuron proportional to their representation in uninfected ganglia. In murine trigeminal ganglia harvested during HSV latency, 25% of HSV-1 LAT and 4% of HSV-2 LAT expressing neurons were A5-positive, while 12% of HSV-1 LAT and 42% of HSV-2 LAT-expressing neurons were KH10-positive. A similar difference was observed in murine dorsal root ganglia. These differences could not be attributed to differences in LAT expression levels in A5 vs. KH10-positive neurons. Thus, HSV-1 demonstrated a preference for establishment of latency in A5-positive neurons, while HSV-2 demonstrated a preference for establishment of latency in KH10-positive neurons. A chimeric HSV-2 mutant that expresses the HSV-1 LAT exhibited an HSV-1 phenotype, preferentially establishing latency in A5-positive neurons. These data imply that the HSV-1 and HSV-2 LAT regions influence the ability of virus to establish latency in different neuronal subtypes. Because this same chimeric virus has a characteristic HSV-1 reactivation phenotype, this further suggests that LAT-influenced establishment of latency in specific neuronal subtypes could be an important part of the mechanism by which LAT influences viral reactivation phenotypes.