Human immunodeficiency virus nucleocapsid protein polymorphisms modulate the infectivity of RNA packaging mutants.
The nucleocapsid protein (NC) of retroviruses is involved in viral RNA packaging and initiation of reverse transcription. NC also mediates interactions between Gag and actin filaments. We found that residues at the amino terminus of NC are involved in efficient actin binding. When alanine residues were substituted for the arginine and lysine at positions 10 and 11 of NC in HIV(NL4-3), these mutations decreased actin binding but had only a modest effect on virus infectivity. A similarly mutated virus based on the HXB2 clone of HIV was not infectious. Mutational analysis of NL4-3 NC residues demonstrated that NC polymorphisms modulated the phenotype of NC mutations. Conservative amino acid differences between HXB2 and NL4-3 NCs were sufficient to explain the difference in infectivity of viruses carrying the R10A and K11A mutations.
Krogstad
Paul
P
Department of Pediatrics, University of California, Los Angeles School of Medicine, Los Angeles, California 90095-1732, USA. pkrogstad@mednet.ucla.edu
Geng
Yong-Zhi
YZ
Rey
Osvaldo
O
Canon
Jude
J
Ibarrondo
F Javier
FJ
Ackerson
Bradley
B
Patel
Jignesh
J
Aldovini
Anna
A
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology*
D000199:Actins; D015683:Gene Products, gag; D012367:RNA, Viral