Conditional infectivity of a human immunodeficiency virus matrix domain deletion mutant.
We constructed a human immunodeficiency virus (HIV) matrix (MA) deletion mutant by deletion of about 80% of the HIV type 1 Gag MA domain but retaining myristylation and proteolytic processing signals. The effects of this deletion matrix (dl.MA) mutant on HIV particle assembly, processing, and infectivity were analyzed. Surprisingly, the dl.MA mutant still could assemble and process virus particles, had a wild-type (wt) retrovirus particle density, and possessed wt reverse transcriptase activity. RNase protection experiments showed that dl.MA mutant particles preferentially packaged viral genomic RNA. When both mutant and wt particles were pseudotyped with an amphotropic murine leukemia virus envelope protein, mutant infectivity was about 10% of wt level. In contrast, infectivity of the dl.MA mutant was 1,000-fold less than that of wild-type when mutant and wt particles were pseudotyped with the HIV envelope protein. Protein analyses of pseudotyped virions indicated that there were no major differences between mutant and wt viruses in the efficiency of amphotropic murine leukemia virus envelope protein incorporation. In contrast, there was a reduction in the amount of mutant particle-associated HIV envelope protein gp120. Our results suggest that an intact HIV matrix domain is not absolutely required for reverse transcription, nuclear localization, or integration but is necessary for appropriate HIV envelope protein function.
Wang
C T
CT
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201-3098.
Zhang
Y
Y
McDermott
J
J
Barklis
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D015683:Gene Products, gag / Q000235:genetics*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011499:Protein Processing, Post-Translational; D012367:RNA, Viral / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D017384:Sequence Deletion; D014763:Viral Matrix Proteins / Q000235:genetics*; D014771:Virion / Q000302:isolation & purification; D014774:Virulence
D015683:Gene Products, gag; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase