Herpes simplex virus type 2 glycoprotein G-negative clinical isolates are generated by single frameshift mutations.
Herpes simplex virus (HSV) codes for several envelope glycoproteins, including glycoprotein G-2 (gG-2) of HSV type 2 (HSV-2), which are dispensable for replication in cell culture. However, clinical isolates which are deficient in such proteins occur rarely. We describe here five clinical HSV-2 isolates which were found to be unreactive to a panel of anti-gG-2 monoclonal antibodies and therefore considered phenotypically gG-2 negative. These isolates were further examined for expression of the secreted amino-terminal and cell-associated carboxy-terminal portions of gG-2 by immunoblotting and radioimmunoprecipitation. The gG-2 gene was completely inactivated in four isolates, with no expression of the two protein products. For one isolate a normally produced secreted portion and a truncated carboxy-terminal portion of gG-2 were detected in virus-infected cell medium. Sequencing of the complete gG-2 gene identified a single insertion or deletion of guanine or cytosine nucleotides in all five strains, resulting in a premature termination codon. The frameshift mutations were localized within runs of five or more guanine or cytosine nucleotides and were dispersed throughout the gene. For the isolate for which a partially inactivated gG-2 gene was detected, the frameshift mutation was localized upstream of but adjacent to the nucleotides coding for the transmembranous region. Thus, this study demonstrates the existence of clinical HSV-2 isolates which do not express an envelope glycoprotein and identifies the underlying molecular mechanism to be a single frameshift mutation.
Liljeqvist
J A
JA
Department of Virology, University of Göteborg, S-413 46 Göteborg, Sweden. jan-ake.liljeqvist@microbio.gu.se
Svennerholm
B
B
Bergström
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral; D004797:Enzyme-Linked Immunosorbent Assay; D016368:Frameshift Mutation; D017353:Gene Deletion; D005814:Genes, Viral; D006558:Herpes Genitalis / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D011817:Rabbits; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification
D004279:DNA, Viral; D014759:Viral Envelope Proteins; C045464:glycoprotein G, herpes simplex virus type 2