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Capsid stability and replication of human immunodeficiency virus type 1 are influenced critically by charge and size of Gag residue 183

Bernd Leschonsky^,

Christine Ludwig

Institute of Medical Microbiology and Hygiene, Molecular Microbiology and Gene Therapy, University of Regensburg, 93053 Regensburg, Germany

Correspondence
Ralf Wagner
ralf.wagner{at}klinik.uni-regensburg.de

Structural data support a model where – following proteolytic cleavage – the amino-terminal domain of human immunodeficiency virus type 1 (HIV-1) capsid protein refolds into a -hairpin/helix tertiary structure that is stabilized by a buried salt bridge forming between the positively charged primary imino group of a proline residue and the negatively charged carboxyl group of a conserved aspartate. In order to evaluate the contribution of either side-chain length or charge to the formation of infectious virus capsids, aspartate 183 was substituted for glutamate or asparagine in the viral context. It was found that both modifications abolished infectivity of the corresponding viruses in permissive T lymphocytes, although none of particle assembly and release, RNA encapsidation, incorporation of Env glycoproteins and packaging of cyclophilin A were impaired. However, whereas biophysical analyses of mutant virions yielded wild-type-like particle sizes and densities, electron microscopy revealed aberrant core morphologies that could be attributed to either increased (D183N) or reduced (D183E) capsid stability. Although the two amino acid substitutions had opposing effects upon core stability, both mutants were shown to exhibit a severe block in early reverse transcription, underscoring the importance of correct salt-bridge formation for early steps of virus replication.

A table showing primers used to amplify intermediates of reverse transcription is available in JGV Online.

These authors contributed equally to this work.

Present address: Abbott Ireland, Diagnostics Division, Finisklin Business Park, Sligo, Ireland.

This article has been cited by other articles:

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