Characterization of replication defects induced by mutations in the basic domain and C-terminus of HIV-1 matrix.
Extensive mutagenesis has defined distinct functional domains in the HIV-1 matrix domain (MA). In an attempt to more clearly define functions of regions of MA which affect viral entry, we analyzed mutations in the N-terminal basic and the C-terminal helical domains. Deletions of 8-10 amino acid residues of the C-terminal fifth helix of MA resulted in viruses that were only mildly defective in infectivity and fusion. The defect exhibited by these mutations could largely be attributed to a reduction in levels of viral envelope incorporated into mature virions. Truncation of the gp41 cytoplasmic tail (gp41CT) could rescue the phenotype of one of these mutants. In contrast, mutations of multiple basic residues in the N-terminus of MA were severely defective in both infectivity and fusion. While these mutations induce severe envelope incorporation defects, they also result in virus crippled at a post-entry step, since truncation of the gp41CT could not rescue the infectivity defect.
Bhatia
Ajay K
AK
Division of Molecular Oncology, Departments of Medicine and Molecular Microbiology, Washington University Medical Center, St. Louis, MO, USA.
Campbell
Nancy
N
Panganiban
Antonito
A
Ratner
Lee
L
D024361:Amino Acids, Basic / Q000235:genetics; D002460:Cell Line; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014771:Virion / Q000737:chemistry; D019065:Virus Assembly / Q000235:genetics; D053586:Virus Internalization; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000032:analysis / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
D024361:Amino Acids, Basic; D015488:HIV Antigens; D015700:HIV Envelope Protein gp41; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1
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