Virus particle core defects caused by mutations in the human immunodeficiency virus capsid N-terminal domain

Isabel Scholz, Brian Arvidson, Doug Huseby, Eric Barklis

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1470-1479
Number of pages10
JournalJournal of Virology
Volume79
Issue number3
DOIs
StatePublished - Feb 2005

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capsid
Capsid
Human immunodeficiency virus
virion
histidine
Histidine
Virion
Cyclophilin A
HIV
cyclophilins
mutation
Mutation
Capsid Proteins
Human immunodeficiency virus 1
coat proteins
viruses
mutants
HIV-1
Viruses
Virus Internalization

ASJC Scopus subject areas

  • Immunology

Cite this

Virus particle core defects caused by mutations in the human immunodeficiency virus capsid N-terminal domain. / Scholz, Isabel; Arvidson, Brian; Huseby, Doug; Barklis, Eric.

In: Journal of Virology, Vol. 79, No. 3, 02.2005, p. 1470-1479.

Research output: Contribution to journalArticle

Scholz, Isabel ; Arvidson, Brian ; Huseby, Doug ; Barklis, Eric. / Virus particle core defects caused by mutations in the human immunodeficiency virus capsid N-terminal domain. In: Journal of Virology. 2005 ; Vol. 79, No. 3. pp. 1470-1479.
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