STRUCTURE AND FUNCTION OF THE MURINE CYTOMEGALOVIRUS SGG1 GENE - A DETERMINANT OF VIRAL GROWTH IN SALIVARY-GLAND ACINAR-CELLS

The salivary gland has long been recognized as an important target org an for cytomegalovirus replication in the infected host. A viral gene, denoted sgg1, plays an important role for replication in the salivary gland even though it is dispensable for growth in other organs or in cultured cells. The nucleotide sequence of this gene and of cDNA clone s representing two spliced transcripts (1.5 and 1.8 kb in size) has be en determined. The more abundant 1.5-kb transcript contains a 312-amin o-acid (aa) open reading frame (ORF) and encodes the corresponding 37- kDa protein (Sgg1) when expressed in transfected COS-7 cells. The 1.8- kb transcript initiates upstream of the 1.5-kb transcript and contains a 108-aa ORF in addition to the 312-aa ORF. This longer cDNA also enc odes the 37-kDa protein Sgg1, although at lower abundance than the 1.5 -kb cDNA. Sgg1 localizes to the cytoplasm of COS-7 cells, which is con sistent with the predicted structural characteristics of the 312-aa OR F:a type 1 integral membrane protein. During viral infection, expressi on of both sgg1 transcripts is highest at early times (8 to 12 h) afte r infection; only the 1.5-kb transcript is present, at low levels, lat e in infection. A recombinant virus, RM868, carrying a lacZ-gpt insert ion within sgg1, fails to express Sgg1 protein and exhibits reduced gr owth in the salivary gland. RM868 retains the capacity to disseminate in the infected mouse and to enter serous acinar cells, although it fa ils to replicate efficiently in this cell type. These results suggest that sgg1 is critical for high levels of viral replication in the sali vary gland.