MHC immunoevasins: protecting the pathogen reservoir in infection

Alteration of antigen recognition by T cells as result of insufficient major histocompatibility complex (MHC)-dependent antigen-presenting function has been observed in many cases of infections, particularly in in vitro systems. To hide themselves from an efficient immune response, pathogens may act on MHC-related functions at three levels: (i) by limiting the number of potential antigens that can be presented to naive T cells; (ii) by synthesizing proteins which directly affect MHC cell-surface expression; and (iii) by altering the normal intracellular pathway of peptide loading on MHC. Here, we review examples of pathogens' action on each single step of MHC function and we suggest that the result of these often synergistic actions is both a limitation of the priming of naive T cells and, more importantly, a protection of the pathogen's reservoir from the attack of primed T cells. The above mechanisms may also generate a skewing effect on immune effector mechanisms, which helps preserving the reservoir of infection from sterilization by the immune system

Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

Different linkages in the long and short regions of the genomes of duck enteritis virus Clone-03 and VAC Strains

<p>Abstract</p> <p>Background</p> <p>Duck enteritis virus (DEV) is an unassigned member in the family <it>Herpesviridae</it>. To demonstrate further the evolutionary position of DEV in the family <it>Herpesviridae</it>, we have described a 42,897-bp fragment. We demonstrated novel genomic organization at one end of the long (L) region and in the entire short (S) region in the Clone-03 strain of DEV.</p> <p>Results</p> <p>A 42,897-bp fragment located downstream of the <it>LOFR11 </it>gene was amplified from the Clone-03 strain of DEV by using 'targeted gene walking PCR'. Twenty-two open reading frames (ORFs) were predicted and determined in the following order: 5'<it>-LORF11-RLORF1</it>-<it>ORF1</it>-<it>ICP4</it>-<it>S1-S2-US1-US10-SORF3-US2-MDV091.5-like-US3-US4-US5-US6-US7-US8-ORFx-US1-S2-S1-ICP4 </it>-3'. This was different from that of the published VAC strain, both in the linkage of the L region and S region, and in the length of the US10 and US7 proteins. The <it>MDV091.5-like </it>gene, <it>ORFx </it>gene, <it>S1 </it>gene and <it>S2 </it>gene were first observed in the DEV genome. The lengths of DEV US10 and US7 were determined to be 311 and 371 amino acids, respectively, in the Clone-03 strain of DEV, and these were different from those of other strains. The comparison of genomic organization in the fragment studied herein with those of other herpesviruses showed that DEV possesses some unique characteristics, such as the duplicated US1 at each end of the US region, and the US5, which showed no homology with those of other herpesviruses. In addition, the results of phylogenetic analysis of ORFs in the represented fragment indicated that DEV is closest to its counterparts VZV (<it>Varicellovirus</it>) and other avian herpesviruses.</p> <p>Conclusion</p> <p>The molecular characteristics of the 42,897-bp fragment of Clone-03 have been found to be different from those of the VAC strain. The phylogenetic analysis of genes in this region showed that DEV should be a separate member of the subfamily <it>Alphaherpesvirinae</it>.</p