CHARACTERIZATION OF RHESUS CYTOMEGALOVIRUS GENES ASSOCIATED WITH ANTIVIRAL SUSCEPTIBILITY

Studies were initiated to determine whether rhesus cytomegalovirus (Rh CMV)-infected macaques could serve as an animal model for evaluating a nti-CMV compounds, as macaques have a naturally occurring CMV that is similar to human CMV (HCMV). Utilizing plaque reduction assays, RhCMV was tested for anti-viral susceptibility. By these assays, RhCMV displ ayed anti-viral susceptibility to ganciclovir al a 50% effective dose (ED50) of 0.8 mu M, acyclovir at an ED50 of 15 mu M, and foscarnet at an ED50 of 250 mu M. By Southern blot analysis with HCMV UL97 (phospho transferase) and DNA polymerase (pol) genes as probes, we isolated vir al DNA fragments that strongly hybridized. DNA sequence analysis of th ese DNA fragments revealed two open reading frames with homology to HC MV UL97 and DNA polymerase. Steady-state RNA analysis revealed that th e RhCMV UL97 homologue and pol genes are transcribed as early late and early genes, respectively. Comparison against HCMV showed the RhCMV U L97 homologue exhibits 54.4% amino acid (aa) sequence identity to HCMV UL97 and the RhCMV DNA polymerase 59.2% aa sequence identity to HCMV DNA polymerase. Results from anti-viral assays and molecular character ization of these two viral genes suggest that RhCMV-iniected rhesus ma caques should serve as an excellent animal model for evaluating future anti-CMV compounds. (C) 1998 Academic Press.