Gammaherpesvirus Latency Differentially Impacts the Generation of Primary versus Secondary Memory CD8 T Cells during Subsequent Infection

Unlike laboratory animals, humans are infected with multiple pathogens, including the highly prevalent herpesviruses. The pur-pose of these studies was to determine the effect of gammaherpesvirus latency on T cell number and differentiation during sub-sequent heterologous viral infections. Mice were first infected with murine gammaherpesvirus 68 (MHV68), a model of Epstein-Barr virus (EBV) infection, and then after latency was established, they were challenged with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV). The initial replication of LCMVwas lower in latently infected mice, and the matu-ration of dendritic cells was abated. Although the number of LCMV-specific effector CD8 T cells was not altered, they were skewed to a memory phenotype. In contrast, LCMV-specific effector CD4 T cells were increased in latently infected mice com-pared to those in mice infected solely with LCMV.When the memory phase was reached, latently infected mice had an LCMV-specific memory T cell pool that was increased relative to that found in singly infected mice. Importantly, LCMV-specific mem-ory CD8 T cells had decreased CD27 and increased killer cell lectin-like receptor G1 (KLRG1) expression. Upon secondary challenge, LCMV-specific secondary effector CD8 T cells expanded and cleared the infection. However, the LCMV-specific sec-ondary memory CD8 T cell pool was decreased in latently infected animals, abrogating the boosting effect normally observed following rechallenge. Taken together, these results demonstrate that ongoing gammaherpesvirus latency affects the number and phenotype of primary versus secondary memory CD8 T cells during acute infection