Herpesvirus latency differentially impacts primary versus secondary memory T cell pools (P6119)

Abstract

Abstract Unlike laboratory animals, humans are infected with multiple pathogens, including the highly prevalent herpesviruses. The purpose of these studies was to determine the effect of herpesvirus latency on T cell number and differentiation during subsequent heterologous viral infections. Mice were infected with murine Gammaherpesvirus 68 (MHV68), a model of Epstein-Barr infection, and then after latency was established, infected with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV). This resulted in increased LCMV-specific effector CD4+ T cells compared to mice infected only with LCMV. Although the number of LCMV-specific effector CD8+ T cells was not altered, they were skewed to a memory phenotype. When the memory phase was reached, mice that were infected with both viruses had a memory T cell pool that was increased relative to that found in singly infected mice. Importantly, LCMV-specific memory CD8+ T cells had altered CD27 and KLRG1 expression. Upon secondary challenge the LCMV-specific effector CD8+ and CD4+ T cell pools expanded and cleared the infection. When the secondary memory pool was established, mice that were also infected with MHV68 had decreased numbers of LCMV-specific CD8+ T cells and these cells were skewed to an effector-memory phenotype. Taken together these results demonstrate that acute viral infection in the context of ongoing latency affects the number and phenotype of primary versus secondary memory CD8+ T cells.