CYTOMEGALOVIRUS MISSING CAPSID PROTEIN IDENTIFIED AS HEAT-AGGREGABLE PRODUCT OF HUMAN CYTOMEGALOVIRUS UL46

Capsids of human and simian strains of cytomegalovirus (HCMV and SCMV, respectively) have identified counterparts for all but one of the pro tein components of herpes simplex virus (HSV) capsids. The open readin g frames (ORFs) for the CMV and HSV counterpart proteins are positiona lly homologous in the two genomes. The HSV capsid protein without a re cognized counterpart in CMV is VP19c, a 50-kDa element of the intercap someric ''tripler.'' VP19c is encoded by HSV ORF UL38, whose positiona l homolog in the HCMV genome is UL46, The predicted protein product of HCMV UL46, 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. To identify and learn more about the protei n encoded by HCMV UL-46, we have expressed it in insect cells from a r ecombinant baculovirus and tested for its presence in CMV-infccted hum an cells and virus particles with two UL46-specific antipeptide antise ra. Results presented here show that this HCMV protein (i) has a size of approximate to 30 kDa as expressed in both recombinant baculovirus- infected insect cells and HCMV-infected human cells; (ii) has a homolo g in SCMV; (iii) is a capsid component and is present in a 1:2 molar r atio with the minor capsid protein (mCP), encoded by UL85; and (iv) in teracts with the mCP, which is also shown to interact with itself as d emonstrated by the GAL4 two-hybrid system; and (v) aggregates when hea ted and does not enter the resolving gel during sodium dodecyl sulfate -polyacrylamide gel electrophoresis (SDS-PAGE), a characteristic that accounts for it eluding detection until now. We call this protein the mCP-binding protein, and on the basis of the characteristics that it s hares with HSV VP19c. we conclude that the HCMV mCP-binding protein is the functional as well as genetic homolog of HSV VP19c.