CD8α Dendritic Cells Drive Establishment of HSV-1 Latency

Abstract

It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG) of wild-type (WT) C57BL/6 versus CD8α−/− (lack functional CD8 T cells and CD8α+ DCs), CD8β−/− (have functional CD8α+ T cells and CD8α+ DCs), and β2m−/− (lack functional CD8 T cells but have CD8α+ DCs) mice as well as BXH2 (have functional CD8 T cells but lack CD8α+ DCs) versus WT C3H (have functional CD8α T cells and CD8α+ DCs) mice. We also determined whether the phenotype of CD8α−/− and BXH2 mice could be restored to that of WT mice by adoptive transfer of WT CD8+ T cells or bone marrow (BM) derived CD8α+ DCs. Our results clearly demonstrate that CD8α DCs, rather than CD8 T cells, are responsible for enhanced viral latency and recurrences.

CD8 + T Cells Play a Bystander Role in Mice Latently Infected with Herpes Simplex Virus 1

“…ϩ DCs enhance viral latency and recurrence in infected mice (22,28). Collectively, then, our data suggest that CD8␣…”

“…Plaque-purified virulent HSV-1 strain McKrae (wild type; LAT ϩ ), avirulent strain RE (wild type; LAT ϩ ) (33), and dLAT2903 (virulent; LAT Ϫ ) were grown in rabbit skin (RS) cell monolayers in minimal essential medium (MEM) containing 5% fetal calf serum (FCS), as described previously (9,28,34). HSV-1 strain RE was a gift from Robert Hendricks, University of Pittsburgh.…”

“…DCs are classified into several subsets, based on their cell surface phenotypes, locations of residence, and functional differences (27). We previously investigated whether CD8␣ ϩ DCs (28). In these studies, we showed that TG from CD8␣ Ϫ/Ϫ mice had significantly lower latency levels than those from wt, ␤ 2 m Ϫ/Ϫ , or CD8␤ Ϫ/Ϫ mice.…”

“…DNAs were isolated from homogenized individual TG as we described previously (28). PCR analyses were done using gB-specific primers and probe (forward primer, 5=-AACGCGACGCACATCAAG-3=; reverse primer, 5=-CT GGTACGCGATCAGAAAGC-3=; and probe, 5=-6-carboxyfluorescein [FAM]-CAGCCGCAGTACTACC-3=).…”

“…RNAs were extracted from latent TG as we described previously (28,36,37). RT-PCR analyses were done using (i) LAT-specific primers (forward primer, 5=-GGGTGGGCTCGTGTTACAG-3=; reverse primer, 5=-GGACGGGTAAGTAACAGAGTCTCTA-3=; and probe, 5=-FAM-ACACCAGCCCGTTCTTT-3=) and (ii) PD-1-specific prim-ers (Mm00435532_m1; ABI).…”