The guinea pig cytomegalovirus (GPCMV) co-linear gene and potential functional homolog of HCMV UL84 (GP84) was investigated. The GP84 gene had delayed early transcription kinetics and transient expression studies of GP84 protein (pGP84) demonstrated that it targeted the nucleus and co-localized with the viral DNA polymerase accessory protein as described for HCMV pUL84. Additionally, pGP84 exhibited a transdominant inhibitory effect on viral growth as described for HCMV. The inhibitory domain could be localized to a minimal peptide sequence of 99 aa. Knockout of GP84 generated virus with greatly impaired growth kinetics. Lastly, the GP84 ORF was capable of complementing for the loss of the UL84 coding sequence in a chimeric HCMV. Based on this research and previous studies we conclude that GPCMV is similar to HCMV by encoding single copy co-linear functional homologs of HCMV UL82 (pp71), UL83 (pp65) and UL84 genes.
Bibliographical noteFunding Information:
We thank Joseph Sweet for technical assistance with the Western blot. We are grateful for the generous gift of the HCMV (Towne) BAC from Gabi Hahn (University of Munich, Germany). Research funding was supported by a MMF grant to AM and NIH grants (HD038416 and 044864) to MS.
- Bacterial artificial chromosome (BAC)
- Congenital infection
- Guinea pig
- Transdominant inhibition