Either a CD4+or CD8+T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice

Abstract

Following ocular infection of normal mice, herpes simplex virus type 1 (HSV-1) establishes a latent infection in the trigeminal ganglia (TG) with the complete absence of detectable infectious virus. In this study, the role of CD4+and CD8+T cell dependent immune responses is examined in relation to clearing infectious virus from the TG following HSV-1 ocular challenge. Nude mice, which lack T cells, and MHCo/omice, which lack both MHC class I and MHC class II, were challenged ocularly with wild-type HSV-1. Over 70% of the TG from mice surviving the infection contained infectious virus, indicative of a chronic infection in these TG, rather than a latent infection. No infectious virus was detected in TGs from infected C57BL/6 parental mice. Ocular challenge of CD4o/oAβo/o, CD8o/oor β2mo/omice resulted in latent rather than chronic infection. Similarly, when C57BL/6 mice were depleted for CD4+or CD8+T cells from 4 days before ocular challenge to 26 days after ocular challenge, no free virus was detected in TGs of challenged mice. In contrast, when mice were depleted of both their CD4+and CD8+T cells, over 90% of TGs were positive for free virus, suggesting that the lack of virus clearance was due to the combined lack of both CD4+T cells and CD8+T cells (i.e. in the presence of either CD4+T cells or CD8+T cells alone all of the infectious virus was cleared and latency was established).