1887

Abstract

To better understand the role of the M2 protein of the murine herpes virus strain 68 (MHV-68) , B-lymphocyte-restricted, M2-transgenic mice were constructed. The transgenic mice contained normal B-cell subpopulations in bone marrow, lymph nodes and spleen. After immunization with sheep red blood cells, spleens from M2-transgenic mice had increased germinal centres. Transgenic mice responded to the T-cell-dependent antigen keyhole limpet haemocyanin (KLH) with higher levels of secondary IgM and IgG2a antibodies than WT mice. Normal and M2-transgenic mice were infected with WT and M2 frame-shift mutant (M2FS) MHV-68 viruses. The pathogenesis of M2-transgenic mice infected with the M2-deficient mutant virus did not revert to that observed upon infection of normal mice with WT virus. However, the higher reactivation levels late after M2-transgenic mice were infected with WT virus reflected the importance of M2 as a target for the immune response, and thus with an impact on the establishment of latency. Finally, there was markedly less apoptosis in B-cells from M2-transgenic mice infected with either WT or M2FS mutant than from similarly infected WT mice, consistent with the published inhibitory influence of M2 on apoptosis . Thus, M2 provides a strategy to increase the pool of germinal centre B-cells through inhibition of apoptosis in the infected cell.

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2013-07-01
2019-10-21
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