GENETIC DIVERSITY AMONG RHESUS ENTERIC CALICIVIRUSES

Tulane University Of Louisiana, New Orleans LA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Noroviruses (NV) are important human pathogens, however NV research has been long time hampered by the lack of an efficient tissue culture or animal model. Recently we reported the discovery of a cultivable calicivirus (Tulane virus;TV). Preliminary results obtained through our ongoing studies show close similarities between TVs and NVs in respect to their phylogeny, epidemiology and histo-blood group antigen (HBGA) binding that make the TV system a promising model for human NV gastroenteritis. In this study 325 randomly selected stool samples collected from TNPRC rhesus macaques were tested for the presence of caliciviruses by using a modified degenerated primer set (P289/P290) targeting conserved amino acid motifs in the calicivirus RNA dependent RNA polymerases (RdRp). Thirty six (11%) of the 325 stools samples tested yielded TV specific sequences, indicating that TVs are endemic in the TNPRC colony. According to phylogenetic analysis, the 36 TV isolates can be classified into two genogroups and at least four genetic types. Interestingly, none of the strains were identical to the prototype TV that was isolated from the same colony in 2004. Such wide genetic diversity among rhesus enteric caliciviruses indicates that the epidemiology and evolution of TVs in the TNPRC colony are similar to those of human NVs, possibly associated with wide HBGA repertoire of the host and immune pressure (herd immunity). Thus, rhesus enteric caliciviruses could be used as a model for the evolution and epidemiology of human NVs. The discovery of TV genetic diversity with the tissue culture adaptability of these viruses is important because it opens the avenue for studying the relationship between genetic variation and serotypes (antigenic types) with applications to NV vaccine and diagnostic assay development.