Virus particle core defects caused by mutations in the human immunodeficiency virus capsid N-terminal domain.
The N-terminal domains (NTDs) of the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein have been modeled to form hexamer rings in the mature cores of virions. In vitro, hexamer ring units organize into either tubes or spheres, in a pH-dependent fashion. To probe factors which might govern hexamer assembly preferences in vivo, we examined the effects of mutations at CA histidine residue 84 (H84), modeled at the outer edges of NTD hexamers, as well as a nearby histidine (H87) in the cyclophilin A (CypA) binding loop. Although mutations at H87 yielded infectious virions, mutations at H84 produced assembly-competent but poorly infectious virions. The H84 mutant viruses incorporated wild-type levels of CypA and viral RNAs and showed nearly normal signals in virus entry assays. However, mutant CA proteins assembled aberrant virus cores, and mutant core fractions retained abnormally high levels of CA but reduced reverse transcriptase activities. Our results suggest that HIV-1 CA residue 84 contributes to a structure which helps control either NTD hexamer assembly or the organization of hexamers into higher-order structures.
Scholz
Isabel
I
Vollum Institute and Department of Microbiology, Mail Code L220, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201-3098, USA.
Arvidson
Brian
B
Huseby
Doug
D
Barklis
Eric
E
D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D021984:Cyclophilin A / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity / Q000648:ultrastructure; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D013329:Structure-Activity Relationship; D014771:Virion / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000648:ultrastructure*; D019065:Virus Assembly
D036022:Capsid Proteins; D021984:Cyclophilin A