Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. We have used a combination of biochemical and immunological techniques to demonstrate that this protein, called the smallest capsid protein in human cytomegalovirus, is encoded by a previously unidentified 225-bp open reading frame (ORF) located between ORFs UL48 and UL49. Resistance to the 2-bromo analog (BDCRB) has been mapped to the UL89 open reading frame (ORF), and this gene product was proposed as the viral target of the benzimidazole nucleosides. The predicted protein product of HCMV UL4A6, however, has essentially no amino acid sequence similarity to HSV VP19c, is only two-thirds as long, and was not recognized as a component of CMV capsids. A mutation in this protein which prevented incorporation of [3H]myristic acid also altered the detergent solubility and intracellular distribution of the protein when it was expressed in transfected cells. To develop strategies to prevent and treat HCMV infection, it is crucial to understand the early interactions between the virus and its host cell that lead to the establishment and progression of the virus replication cycle. This configuration closely parallels the disulfide bond configuration of herpes simplex type 2 (HSV-2) gB (N.
Norais, D. Acad. Glycoprotein B (gB) homologues are highly conserved within the herpesvirus family. The smallest UL37 gene product, pUL37x1, encodes a potent antiapoptotic function called viral mitochondrion-localized inhibitor of apoptosis (vMIA) (20).