Herpes simplex virus type 1 UL46 and UL47 deletion mutants lack VP11 and VP12 or VP13 and VP14, respectively, and exhibit altered viral thymidine kinase expression

Abstract

The gene products of herpes simplex virus type 1 UL46 and UL47 enhance the efficiency of aTIF (VP16)-mediated a gene expression through an unknown mechanism of action. To further characterize the function of the UL46-and UL47-encoded proteins during virus infection, a series of isogenic herpes simplex virus type 1 strain F-derived UL46 and UL47 single-deletion mutants and a UL46/47 double-deletion mutant were constructed and compared with the wild type. Analysis of purified virions obtained from the UL46 deletion mutant showed for the first time that UL46 encoded the virion tegument phosphoproteins VP11 and VP12 (VP11/12). Similar analyses of the UL47 deletion mutants confirmed an earlier report by McLean et al. that UL47 also encoded two virion tegument phosphoproteins, VP13 and VP14 (VP13/14) (G. McLean, F.

The herpes simplex virus type 1 particle: structure and molecular functions

“…This product seems not to be essential for growth of virus in cell culture. Recent calculations (268) indicate that there are close to 1300 molecules per virion, which is considerably more than previously estimated (86).…”

“…Although the existence of two structural phosphoproteins designated VPll and VP12 with molecular weights of 93K and 87K, respectively, has been known for a long time (124, 232), information about them has been scarce until deletion mutants were recently made by Zhang & Mcfiight. These authors were thus able to show that both proteins are present in the tegument and are encoded by gene UL46 (268). It was suggested that VPll and VP12 were two differently phosphorylated forms of the same primary translation product.…”

“…Initiation of translation from different inframe AUG codons in the mRNA is a possibility which has not yet been tested (152). VP13/14 is an abundant protein present in approximately 1800 copies per virion (86,268). Homologues of the UL47 protein are identified as VP8 and glycoprotein gpl0 in bovine herpesvirus and equine herpesviruses 1 and 4, respectively (26, 259).…”

“…The product is the major tegument protein 65KTIF (VP16). It has recently been proposed that 65KTIF is associated with V P l l / 12 and VP13/14 in the virion (268). Both sets of proteins may modulate the transinducing activity in transient expression systems (147), but in the context of virus only the UL47 proteins (VPl3 / 14) seem to have an effect (267).…”

Immune response to the herpes simplex type 1 regulatory proteins ICP8 and VP16 in infected persons

“…This report demonstrates that the major tegument protein VP16 and the major DNA binding protein ICP8 of HSV-1 are immunogenic in humans, even though a T cell recall response with blood monocytes serving as antigen presenting cells could not be demonstrated in HSV-1 seropositive healthy individuals. This was surprising at first as both proteins are produced in large amounts during infection compared to other proteins [Zhang and McKnight, 1993] and have been shown to be essential for productive viral replication in vivo [Conley et al, 1981;Ace et al, 1989]. It seems likely that if infected cells acted as facultative antigen presenting cells this presentation obviously does not induce long-lasting T cell memory for these antigens.…”