Study on cytomegalovirus: cell tropism, pathogenesis, and induction of protective antibodies.

点击翻译按钮获取中文摘要

In contrast to murine and rat CMVs, guinea pig CMV (GPCMV) crosses the placenta and causes infection in utero, which makes GPCMV animal models useful for studies on the mechanisms of transplacental transmission of CMV. Previously, we reported that the GPCMV stock purchased from the ATCC contained two types of strains, one containing and the other lacking a 1.6 kb locus that encodes human CMV UL128 and UL130 homologs, GP129 and GP131, and that the 1.6 kb locus was required for efficient viral growth in animals but not in cell culture. HCMV UL128/130/131A form a pentamer complex with gH/gL and play a role in the endothelial/epithelial-tropism. In this study, we constructed a BAC containing a GPCMV genome, the virus from which grew normally in guinea pig fibroblast cells GPL. Using the RedET recombination system for BAC, mutations were introduced into each of GP129, GP131, and GP133 ORFs. Although all mutants grew in GPL and epithelial cell line GPC-16 at the level similar to a virus derived from the BAC with the wild-type sequence, they could not infect monocytes/ macrophages. GPCMV was transmittable to fibroblast from infected macrophages by co-culturing. Since macrophages play an important role in dissemination of virus to the organs, the macrophage tropism may associate with efficient viral growth in vivo.