Loss of invariant chain expression with vaccinia virus infection of APC

Abstract

Vaccinia virus (VV) has been used as a vaccine to eradicate smallpox and tested as a vaccine vector for HIV and tumor immunotherapy. The immunoevasive properties of VV, however have raised concerns with respect to the use of this virus in immune deficient patients, the elderly and children. VV infection can disrupt components of both host innate and adaptive immunity. VV infection of antigen presentation cells (APC) perturbs MHC class II‐mediated presentation of peptides, endogenous and exogenous antigens. In monitoring VV infection of human B cell lines, virus infection was observed to dramatically reduce expression of the class II chaperone invariant chain (Ii) in a time dependent manner. By contrast, the surface expression of MHC class II molecules was maintained along with cell viability up to 24h after exposure to virus. A reduction in Ii and class II mRNA levels was detected upon VV infection of APC. Analysis of Ii degradation in VV treated cells, revealed Ii proteolysis contributed to the reduced steady state of Ii levels in these APC. Yet, VV infection of APC altered the expression of lysosomal proteases likely influencing Ii degradation. These results demonstrate that at later stages of VV infection, reduced cellular Ii levels may contribute to defects in class II presentation.