Inclusion of CD80 in HSV Targets the Recombinant Virus to PD-L1 on DCs and Allows Productive Infection and Robust Immune Responses

Kevin R Mott,Arlene H Sharpe,Hadi Maazi,Steven L Wechsler,Pedram Hamrah,Homayon Ghiasi,Mandana Zandian,Omid Akbari,Gordon J Freeman,Sariah J Allen,Lbachir Benmohamed

doi:10.1371/journal.pone.0087617

Abstract

CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC.

Highlights

Dendritic cells (DCs) are bone marrow-derived cells that are involved in antigen capture, processing, and presentation and are the most powerful of the antigen presenting cells (APCs), playing a key role in triggering the immune system against infectious agents [1,2,3,4,5,6]
We have reported that in contrast to bone marrow (BM)-derived DCs from wild type mice, DCs isolated from signal transducers and activators of transcription-1 deficient (STAT1-/-) mice were susceptible to Herpes simplex virus (HSV)-1 replication [10]
In this study we constructed a recombinant derivative of HSV-1 strain McKrae that expresses two complete copies of the murine CD80 gene to examine the effects of CD80 expression on HSV-1 infectivity

Summary

Introduction

Dendritic cells (DCs) are bone marrow-derived cells that are involved in antigen capture, processing, and presentation and are the most powerful of the antigen presenting cells (APCs), playing a key role in triggering the immune system against infectious agents [1,2,3,4,5,6]. DCs perform crucial roles in linking innate and adaptive immunity and play a key role in triggering the immune system against HSV-1 infection [7,8,9]. We have reported that in contrast to bone marrow (BM)-derived DCs from wild type mice, DCs isolated from signal transducers and activators of transcription-1 deficient (STAT1-/-) mice were susceptible to HSV-1 replication [10]. The CD80 and CD86 molecules are expressed by multiple cell types, including B cells, macrophages, DCs, and T cells [12,13,14,15]

Methods

Results

Conclusion