title: Selective B-cell expression of the MHV-68 latency-associated M2 protein regulates T-dependent antibody response and inhibits apoptosis upon viral infection.
abstract: To better understand the role of the M2 protein of the murine herpes virus strain 68 (MHV-68) in vivo, 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 in vitro. Thus, M2 provides a strategy to increase the pool of germinal centre B-cells through inhibition of apoptosis in the infected cell.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: V L
authors.initials: VL
authors.lastname: de Oliveira
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: S C P
authors.initials: SCP
authors.lastname: Almeida
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: H R
authors.initials: HR
authors.lastname: Soares
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: R M E
authors.initials: RME
authors.lastname: Parkhouse
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D018858:Germinal Center; D006433:Hemocyanins / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D018144:Rhadinovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; C577263:M2 protein, murine gammaherpesvirus 68; D014764:Viral Proteins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin