Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells

Abstract

Cytotoxic T lymphocytes (CTL) generated in C57BL/6 (H-2b) mice in response to infection with the serologically distinct herpes simplex virus type 1 (HSV-t) or type 2 (HSV-2) were cross-reactive against target cells infected with either serotype. However, HSV-2-infected cells were shown to be much less susceptible to CTL-mediated lysis, and analysis through the use of HSV-1 x HSV-2 intertypic recombinants mapped the reduced susceptibility to a region contained within 0.82 to 1.00 map units of the HSV-2 genome. The study reported here was undertaken to determine the possible reasons for the reduced susceptibility of HSV-2infected cells to lysis by CTL. Competition for the specific lysis of labeled HSV-1-infected cells by either HSV-1or HSV-2-infected, unlabeled inhibitor cells and frequency analysis of the CTL precursor able to recognize HSV-1and HSV-2-infected cells suggested that the reduced susceptibility of HSV-2-infected cells to lysis could be explained, at least in part, by reduced levels of target cell recognition. A determination of the surface expression of the critical elements involved in target cell recognition by CTL following infection with HSV-1 or HSV-2 revealed that all the major HSV-specific glycoprotein species were expressed. Infection with both HSV-1 and HSV-2 caused a reduction in the expression of the class I H-2 antigens. However, this reduction was much greater following infection with HSV-2. This suggested that one important factor contributing to reduced lysis of HSV-2-infected cells may be the altered or reduced expression of the class I H-2 self-antigens.

Flavivirus infection up-regulates the expression of class I and class II major histocompatibility antigens on and enhances T cell recognition of astrocytes in vitro

“…Since it was established that MHC antigens formed an important part of the antigenic struc-165 ture recognised by T lymphocytes (Zinkernagel and Doherty, 1979;Schwartz, 1986), there "has been great interest in the regulation of MHC antigen expression on potentJal antigen-presenting cells. It is well documented that different virus infections may either inhibit or enhance the expression of MHC antigens, Notably, infection by adenovirus (F~i~lbo et al, 1986), herpes simplex virus type 2 (Jennings et aL, 1985), ectromeiia virus (Gardner et al, 1975) and measles virus (Rager-Zisman et al, 1981) can down-regulate class I MHC antigen expression of their host cells and may make the latter less susceptible to cytotoxic T cells. On the other hand, murine hepatitis virus (Massa et al, 1986;Suzumura et al, 1986), Epstein-Barr virus (McCune et al, 1975, Moloney murine leukemia virus (Flyer et ai., 1985) and Theiler's murine encephalomyelitis virus (Rodriguez et al, 1987) can up-regulate class I and/or class II MHC antigen expression.…”

“…Infection by viruses that down-regulate cell surface MHC antigen expression, on the other hand, results in reduced susceptibility of the infected cells to lysis by virus-specific cytotoxic T cells. Thus it has l~een shown that herpes simplex virus type 2 infection, which down-regulates cell surface MHC expression, reduces the susceptibility of an SV40-and HSV2-double-infectezl targets to lysis by SV40specific Tc cells, as compared to target cells infected with SV40 alone (Jennings et al, 1985). Adenovirus type 5 infection inhibits the cell surface expression of class I MHC antigen via the E3 protein.…”

Human cytomegalovirus in the pancreas of patients with type 2 diabetes: Is there a relation to clinical features, mRNA and protein expression of insulin, somatostatin, and MHC class II?

“…Technical problems or yet unknown variations in the interplay between transcription and translation may be important. However, the fact that diabetic HCMV-positive pancreases expressed class II MNC mRNA more frequently than HCMV-negative diabetic glands may be related to the fact that viruses are known to induce class I and class II expression (Jennings et al 1985;Rosenthal et al 1985;Suzumura et al 1986;Gaulton et al 1989). Islet amyloidosis, the deposition of extracellular IAPP as amyloid within the islets is a morphological indicator lesion for type 2 diabetes in the pancreas (Westermark et al 1987;Clark et al 1990;K16ppel et al 1991).…”

“…Most pancreases from patients with diabetes, however, lack signs of lytic islet cell necrosis, but display changes that are either compatible with autoimmune destruction of the/3-cells, as in type 1 diabetes (K16ppel et al 1991), or B-cell dysfunction, as in type 2 diabetes (K16ppel et al 1991). Yet viruses might still play a role in the pathogenesis of diabetes by either triggering auto-immune B-cell destruction via expression of major histocompatibility complex (MHC) proteins (Bottazzo et al 1985;Jennings et al 1985;Foulis and Farquharson 1986;Suzumura etal, 1986;Campbell etal. 1988) or, alternatively, by persisting in B-cells and impairing their specific function (Oldstone et al 1984;Oldstone 1989).…”

Alteration of intracerebral cytokine production in mice infected with herpes simplex virus types 1 and 2

“…These data are consistent with the supposition that viruses can regulate the expression of MHC molecules leading to either immune evasion or autoimmunity (Maudsley and Pound, 1991). Virusinduced suppression of MHC class I antigen expression has now been demonstrated for adenovirus (Burgert et al, 1987), vaccinia virus (Kohonen-Corish et aL, 1989), HIV (Scheppler et al, 1989) pseudorabies virus (Mellencamp et al, 1991), CMV (murine) (Campbell et al, 1992;Del Valet al, 1992), mouse hepatitis virus (Ceman et al, 1992), and HSV types 1 and 2 (Jennings et al, 1985). The suppression of MHC class II surface expression by human CMV has also been demonstrated (Buchmeier and Cooper, 1989).…”