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. 2007 Feb;81(4):1872-8.
doi: 10.1128/JVI.02110-06. Epub 2006 Dec 6.

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

Todd P Margolis  1 , Yumi Imai, Li Yang, Vicky Vallas, Philip R Krause
Affiliations

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

Todd P Margolis et al. J Virol. 2007 Feb.

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.

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Figures

FIG. 1.
FIG. 1.
Identification of primary sensory neurons latently infected with HSV-1. Sections of infected murine trigeminal ganglia were assayed by both in situ hybridization for HSV-1 LAT (red-labeled nuclei) and immunofluorescent staining with MAbs A5 and KH10 (green-labeled cell bodies) in order to identify the neuronal subpopulations latently infected with HSV-1. In these representative pairs of images, HSV-1 LAT expression is present in A5-positive neurons but not in KH10-positive neurons. Bar = 100 μm.
FIG. 2.
FIG. 2.
Identification of primary sensory neurons latently infected with HSV-2. Sections of infected murine trigeminal ganglia were assayed by both in situ hybridization for HSV-2 LAT (red-labeled nuclei) and immunofluorescent staining with MAbs A5 and KH10 (green-labeled cell bodies) in order to identify the neuronal subpopulations latently infected with HSV-2. In these representative pairs of images, HSV-2 LAT expression is present in KH10-positive neurons but not in A5-positive neurons. Bar = 100 μm.
FIG. 3.
FIG. 3.
Cumulative distribution of LAT in situ hybridization signal intensity in latently infected neurons. Each point represents LAT signal intensity in either A5-positive (red circles) or KH10-positive (blue triangles) trigeminal ganglion neurons 21 days after ocular inoculation with either HSV-1 (A) or HSV-2 (B). Following infection with either HSV-1 or HSV-2 there were no significant differences in LAT signal strength in A5- and KH10-positive neurons. This was true whether the data was analyzed by a two-tailed Student's t test (for HSV-1, P was 0.6; for HSV-2, P was 0.28) or by the Kolmogorov-Smirnov test for equality of distribution (for HSV-1, P was 0.98; for HSV-2, P was 0.19).
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References

    1. Ahmed, M., M. Lock, C. G. Miller, and N. W. Fraser. 2002. Regions of the herpes simplex virus type 1 latency-associated transcript that protect cells from apoptosis in vitro and protect neuronal cells in vivo. J. Virol. 76:717-729. - PMC - PubMed
    1. Bennett, D. L., G. J. Michael, N. Ramachandran, J. B. Munson, S. Averill, Q. Yan, S. B. McMahon, and J. V. Priestly. 1998. A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury. J. Neurosci. 18:3059-3072. - PMC - PubMed
    1. Bloom, D. C. 2004. HSV LAT and neuronal survival. Int. Rev. Immunol. 23:187-198. - PubMed
    1. Dodd, J., and T. M. Jessell. 1985. Lactoseries carbohydrates specify subsets of dorsal root ganglion neurons projecting to the superficial dorsal horn of rat spinal cord. J. Neurosci. 5:3278-3294. - PMC - PubMed
    1. Farrell, M. J., A. T. Dobson, and L. T. Feldman. 1991. Herpes simplex virus latency-associated transcript is a stable intron. Proc. Natl. Acad. Sci. USA 88:790-794. - PMC - PubMed

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