Characterization and immunological analysis of the rhesus cytomegalovirus homologue (Rh112) of the human cytomegalovirus UL83 lower matrix phosphoprotein (pp65).
Rhesus cytomegalovirus (RhCMV) contains two open reading frames (Rh111 and Rh112) that encode proteins homologous to the phosphoprotein 65 (pp65) of the human cytomegalovirus (HCMV) UL83 gene. As HCMV pp65 elicits protective immune responses in infected humans and represents an important vaccination target, one RhCMV homologue of HCMV pp65, pp65-2 (Rh112), was characterized and analysed for its ability to induce host immune responses. Similar to its HCMV counterpart, RhCMV pp65-2 was expressed as a late gene, localized to the nucleus within pp65-2-expressing cells and was present within infectious virions. Longitudinal and cross-sectional studies of pp65-2 immunity in naturally infected rhesus macaques showed that humoral responses to pp65-2 were elicited early during infection, but were not always sustained over time. In contrast, pp65-2-specific T-cell responses, examined by gamma interferon ELISPOT, were broadly detectable in all of the animals studied during primary infection and persisted in the vast majority of RhCMV-seropositive monkeys. Moreover, there was considerable inter-animal variability in the pattern of the immune responses to pp65-2. Together, these results demonstrated that RhCMV pp65-2 exhibited biological and immunological homology to HCMV pp65. Thus, the rhesus macaque model of HCMV persistence and pathogenesis should be relevant for addressing pp65-based vaccine modalities.
Yue
Yujuan
Y
Center for Comparative Medicine, University of California, Davis, County Road 98 and Hutchison Drive, Davis, CA 95616, USA.
Kaur
Amitinder
A
Department of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA 02129, USA.
Zhou
Shan Shan
SS
Center for Comparative Medicine, University of California, Davis, County Road 98 and Hutchison Drive, Davis, CA 95616, USA.
Barry
Peter A
PA
California National Primate Research Center, University of California, Davis, County Road 98 and Hutchison Drive, Davis, CA 95616, USA.|Department of Pathology and Laboratory Medicine, University of California, Davis, County Road 98 and Hutchison Drive, Davis, CA 95616, USA.|Center for Comparative Medicine, University of California, Davis, County Road 98 and Hutchison Drive, Davis, CA 95616, USA.
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D022482:Cytomegalovirus Vaccines / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D022482:Cytomegalovirus Vaccines; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma