Murine Cytomegalovirus Genes Influencing Virus Growth and Tropism for Salivary Gland

Abstract

The salivary gland is an important tissue in cytomegalovirus (CMV) pathogenesis. In the mouse, the salivary gland is the primary site from which virus is transmitted from animal to animal and is also a site of viral persistence and latency. Several murine CMV mutants that exhibit reduced salivary gland tropism have been described in the literature. Many temperature-sensitive mutants grow poorly in the salivary gland; however, the mutations responsible for this poor growth phenotype have not been mapped to particular genes. One variant of the Smith strain of murine CMV, the Vancouver strain, carries a deletion that was rescued by the HindIII E fragment from wild-type murine CMV. The ability to grow in the salivary gland correlated with the expression of a 42-kDa early protein. The salivary gland growth gene-1 (sgg1) of murine CMV has been the most thoroughly characterized determinant of salivary gland tropism. This gene encodes two overlapping transcripts (1.5 and 1.8 kb) which are initiated from different promoters but utilize the same polyadenylation signal. Sequence analysis revealed an open reading frame encoding a putative type 1 integral membrane protein. A 37-kDa protein absent in an sgg1 mutant could be detected in both rescued and wild type virus. The 37 and 42 kDa proteins represent distinct murine CMV proteins that correlate with salivary gland tropism in the mouse. It remains to determine how many other genes are involved in the salivary gland tropism of murine CMV and the mechanism by which these genes act during murine CMV pathogenesis.