Biomedical Sciences Graduate Program | Dean H. Kedes

Biomedical Sciences Graduate Program | Dean H. Kedes

Biomedical Sciences Graduate Program | Dean H. Kedes
Two classes of herpesvirus capsids, designated A and B, were isolated from the nuclei of human cells infected with herpes simplex virus (HSV). After various periods of etching, the proteins remaining intact were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and determined quantitatively by densitometric scanning of the stained gels. The live- attenuated approach has significantly out-performed other vaccine approaches in rhesus monkey models. Procapsids assembled in this way were found to be similar in morphology and in protein composition to procapsids formed in vitro from cell extracts containing HSV-1 proteins. We report that (i) the reduction in the accumulation of gamma(1)34.5 mRNA and protein in cells infected with mutant viruses expressing derepressed ORF P genes reflects the effects of antisense transcription of ORF P rather than a function of ORF P protein, (ii) the attenuated phenotype of the viruses carrying derepressed ORF P genes is due largely to the absence of the gamma(1)34.5 protein, and (iii) the reduction in accumulation of ICP0 and ICP22 requires the expression of ORF P protein. However, following a downshift to the permissive temperature, which allows procapsid maturation to proceed, VP26 was seen to concentrate at intranuclear sites which also contained epitopes specific to mature, angularized capsids. Thomsen, F.

Interestingly, the KSHV Orf50 transactivator can also activate these simian virus promoters, suggesting that there exists a conservation of gene function between the key transcription factors of KSHV and RRV. DNA sequence analysis of the unique long region of the RRV genome reveals it is essentially colinear with KSHV and that it encodes several of the cellular homologues hypothesized to mediate host immune response or alter cell growth and cell cycle regulation (8). The virus is found in the spindle cells and at times in macrophages in the lesion but not the infiltrating T lymphocytes. Hong Zhu (UCLA), immuno-EM and cryo-EM.

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