title: Herpes simplex virus type 2 (HSV-2) establishes latent infection in a different population of ganglionic neurons than HSV-1: role of latency-associated transcripts.
abstract: Herpes simplex virus type 1 (HSV-1) and HSV-2 cause very similar acute infections but differ in their abilities to reactivate from trigeminal and dorsal root ganglia. To investigate differences in patterns of viral infection, we colabeled murine sensory ganglia for evidence of HSV infection and for the sensory neuron marker A5 or KH10. During acute infection, 7 to 10% of HSV-1 or HSV-2 antigen-positive neurons were A5 positive and 13 to 16% were KH10 positive, suggesting that both viruses reach each type of neuron in a manner proportional to their representation in uninfected ganglia. In murine trigeminal ganglia harvested during HSV latency, 25% of HSV-1 latency-associated transcript (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- versus KH10-positive neurons. Thus, HSV-1 demonstrated a preference for the establishment of latency in A5-positive neurons, while HSV-2 demonstrated a preference for the 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. That the same chimeric virus has a characteristic HSV-1 reactivation phenotype 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.
authors.affiliation: F. I. Proctor Foundation, University of California, San Francisco, San Francisco, CA 94143, USA. todd.margolis@ucsf.edu
authors.forename: Todd P
authors.initials: TP
authors.lastname: Margolis
authors.forename: Yumi
authors.initials: Y
authors.lastname: Imai
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Vicky
authors.initials: V
authors.lastname: Vallas
authors.forename: Philip R
authors.initials: PR
authors.lastname: Krause
mesh_terms: D000818:Animals; D005724:Ganglia / Q000821:virology*; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000821:virology*; D013045:Species Specificity; D014774:Virulence; D017735:Virus Latency