Purchase this article with an account.
T.P. Margolis, Y. Imai, K. Apakupakul, P.R. Krause; Differences in the LAT Coding Region Are Responsible gor Differential Latent Infection With Herpes Simplex Virus (HSV) Type 1 and Type 2 . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4302.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Not all ganglionic neurons are equally permissive for latent infection with HSV. Ganglionic neurons identified by Mab A5 are the principle site of latent infection with HSV–1 whereas ganglionic neurons identified by Mab KH10 are the principle site of latent infection with HSV–2. We previously demonstrated that a chimeric HSV–2 that expresses the HSV–1 LAT establishes latency primarily in A5–positive neurons, similar to HSV–1. In the current study we investigated whether a chimeric HSV–1 that expresses the HSV–2 LAT (HSV–1 17+/LAT2) establishes latency primarily in KH10–positive neurons, similar to HSV–2.
Swiss Webster mice were infected by corneal inoculation with either HSV–1 (17+), HSV–1 17+/LAT2, HSV–1 17+/LAT2 rescuant, HSV–2 (MS) or dlsptk, a TK deletion virus. At 21 days post–infection mice were euthanized followed by perfusion with paraformaldehyde. Trigeminal ganglia were then removed, sectioned and assayed by combined in situ hybridization and immunofluorescent staining.
Following ocular inoculation with HSV–1 (17+)/LAT2 45% of the latently infected neurons were KH10+ while only 7% expressed the A5 marker. This distribution was very similar to that observed following inoculation with HSV–2 and significantly different from that observed with HSV–1. In contrast, latent infection with the HSV–1 (17+)/LAT2 rescuant was almost never observed in the KH10+ neuronal population, a pattern similar to that with HSV–1. These results cannot be explained by differential LAT promoter activity in A5+ and KH10+ neurons since following inoculation with dlsptk (an HSV–1 virus incapable of productive infection in neurons), 9% of the latently infected neurons were A5+ and 8% were KH10+, a distribution similar to the representation of these neuronal populations in the trigeminal ganglion.
A chimeric HSV–1 mutant that expresses the HSV–2 LAT establishes latency primarily in KH10–positive neurons, similar to HSV–2. These data imply that a viral function associated with a small portion of the LAT coding region plays a key role in determining the cell tropism of HSV latency.
This PDF is available to Subscribers Only