Lack of effect of mouse adenovirus type 1 infection on cell surface expression of major histocompatibility complex class I antigens

Abstract

It has been proposed that adenoviruses establish and maintain persistent infections by reducing the class I major histocompatibility complex-associated presentation of viral antigens to cytotoxic T lymphocytes, leading to ineffective cell-mediated immunity and impaired clearance of infected cells (W. S. M. Wold and L. R. Gooding, Virology 184:1-8, 1991). Early region 3 of human adenovirus types 2 and 5 encodes a 19-kDa glycoprotein that associates with the class I major histocompatibility complex (MHC) antigens in the endoplasmic reticulum and prevents their maturation and transport to the cell surface. Early region 1A of human adenovirus type 12 encodes a protein that inhibits class I MHC mRNA production at the transcriptional or posttranscriptional processing level. Unlike human adenovirus infections, however, mouse adenovirus type 1 (MAV-1) infection of a variety of cell types did not affect the surface expression of 10 different mouse class I MHC allotypes. MAV-1-infected cells also regenerated cell surface class I MHC antigens following proteolytic removal as efficiently as mock-infected cells. The ability of cells to present antigen to class I MHC (K b )ovalbumin-specific T-cell hybridoma cells was likewise unaltered by MAV-1 infection. Thus, the ability of MAV-1 to persist cannot be explained by the model of reduced class I MHC-associated antigen presentationproposed for human adenoviruses.

The Role of Mouse Adenovirus Type 1 Early Region 1A in Acute and Persistent Infections in Mice

“…It will be interesting to determine what factors allow the virus to persist in the host and what aspects of the immune system are important in maintaining this delicate balance. Previous studies have shown that MAV-1 does not decrease MHC-I surface expression of cultured infected cells (36). Down-regulation of MHC-I has been proposed as a possible mechanism for evading the immune system response by human adenoviruses.…”

Mouse adenovirus type 1 infection of natural killer cell-deficient mice

“…The balance of NK cell activation vs. inhibition can be shifted toward activation of cytotoxicity when NK cells detect target cells expressing reduced levels of MHC class I (reviewed in Biron and Sen, 2007). A previous finding suggests that NK cell recognition of "low MHC class I" cells may not be important for control of MAV-1 infection: MAV-1 infection does not decrease MHC class I expression (Kring and Spindler, 1996). This may reduce the need for NK cell-mediated cytolysis of cells lacking MHC class I. NK cells in mice deficient for MHC class I are defective in target killing (Yokoyama and Kim, 2006).…”

“…Many viruses have mechanisms to downregulate MHC class I, thus protecting them from CD8 + T cell killing, but making them potentially susceptible to NK cell killing. However, MAV-1 does not downregulate MHC class I during infection (Kring and Spindler, 1996). This suggests that the cytotoxic function of NK cells might not be necessary for control of MAV-1 infection.…”

Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

“…For example, one of the first viral immune evasion strategies identified for any virus is downregulation of class I major histocompatibility complex (MHC) antigens on the surface of infected cells by HAdV‐2 . This function of HAdV E3 gp19K is not mimicked by MAdV‐1 infection . The MAdV‐1 E3 proteins do not have sequence similarity to other known proteins.…”

“…MAdV‐1 also causes myocarditis that is accompanied by myocyte and endothelial necrosis when inoculated intraperitoneally or intranasally . Many mouse primary cell types, cell strains, and established cell lines can support MAdV‐1 replication in vitro , including fibroblasts (3T6, 3T12 and L929) , endothelial cells (MBMEC) , preadipocyte cells (3T3‐L1) , epithelial cells (LA‐4, MLE‐12 and MLE‐15; J.B. Weinberg, unpublished), cardiac myocytes macrophages/monocytes , and tumor cells such as lung adenoma (LA‐4), renal adenocarcinoma (RAG) , and rectal carcinoma (CMT‐93) cells .…”