Cytomegalovirus UL128 homolog mutants that form a pentameric complex produce virus with impaired epithelial and trophoblast cell tropism and altered pathogenicity in the guinea pig

- Guinea pig placental trophoblasts require the PC for CMV infection.
- C-terminal deletion mutants (GP129, GP131, or GP133) prevent PC formation.
- Subtle mutations of UL128 homolog (GP129) do not prevent transient PC formation.
- GP129 mutant viruses have modified tropism (renal epithelial and trophoblasts).
- GP129 CC chemokine motif mutation does not prevent PC formation.
- GP129 CC chemokine mutant viruses have modified epi-tropism.
- GP129 CC chemokine motif mutant virus has extended viremia unlike wt virus.

Guinea pig cytomegalovirus (GPCMV) encodes a homolog pentameric complex (PC) for specific cell tropism and congenital infection. In human cytomegalovirus, the PC is an important antibody neutralizing target and GPCMV studies will aid in the development of intervention strategies. Deletion mutants of the C-terminal domains of unique PC proteins (UL128, UL130 and UL131 homologs) were unable to form a PC in separate transient expression assays. Minor modifications to the UL128 homolog (GP129) C-terminal domain enabled PC formation but viruses encoding these mutants had altered tropism to renal and placental trophoblast cells. Mutation of the presumptive CC chemokine motif encoded by GP129 was investigated by alanine substitution of the CC motif (codons 26-27) and cysteines (codons 47 and 62). GP129 chemokine mutants formed PC but GP129 chemokine mutant viruses had reduced epitropism. A GP129 chemokine mutant virus pathogenicity study demonstrated reduced viral load to target organs but highly extended viremia.