Replication-dependent fitness recovery of Human immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein

J. Tőzsér, Sergey Shulenin, Matthew R. Young, Carlton J. Briggs, Stephen Oroszlan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The genetic stability of attenuated Human immunodeficiency virus 1 (HIV-1) variants harbouring mutations (Gly or Lys) of Asn17, the protease-cleavage site of the proximal zinc finger of the nucleocapsid protein, was studied. All possible codons for the Gly mutants were tested as starting sequences. Long-term replication assays revealed that the mutants were unstable; mutations of Gly17 to Arg, Ala, Ser and Cys, as well as a Lys17Asn reversion, were observed. Replication kinetic assays in H9 cells revealed that the replication of Ala, Ser and Arg mutants was improved substantially compared with the Gly variant; the infectivity of Ala17 and Ser17 viruses was equal to, and that of Arg17 was almost equal to, the infectivity of the wild-type virus. Kinetic analysis of the cleavage of oligopeptides representing the corresponding nucleocapsid-cleavage sites revealed that all mutations improved cleavability, in good agreement with the previously proposed role of nucleocapsid cleavage in HIV-1 replication.

Original languageEnglish
Pages (from-to)961-965
Number of pages5
JournalJournal of General Virology
Volume87
Issue number4
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Nucleocapsid Proteins
HIV-1
Nucleocapsid
Mutation
Viruses
Oligopeptides
Zinc Fingers
Virus Replication
Codon
Peptide Hydrolases

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Replication-dependent fitness recovery of Human immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein. / Tőzsér, J.; Shulenin, Sergey; Young, Matthew R.; Briggs, Carlton J.; Oroszlan, Stephen.

In: Journal of General Virology, Vol. 87, No. 4, 04.2006, p. 961-965.

Research output: Contribution to journalArticle

Tőzsér, J. ; Shulenin, Sergey ; Young, Matthew R. ; Briggs, Carlton J. ; Oroszlan, Stephen. / Replication-dependent fitness recovery of Human immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein. In: Journal of General Virology. 2006 ; Vol. 87, No. 4. pp. 961-965.
@article{4d09ebdf4ee14f439feea2a26dc8b5e2,
title = "Replication-dependent fitness recovery of Human immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein",
abstract = "The genetic stability of attenuated Human immunodeficiency virus 1 (HIV-1) variants harbouring mutations (Gly or Lys) of Asn17, the protease-cleavage site of the proximal zinc finger of the nucleocapsid protein, was studied. All possible codons for the Gly mutants were tested as starting sequences. Long-term replication assays revealed that the mutants were unstable; mutations of Gly17 to Arg, Ala, Ser and Cys, as well as a Lys17Asn reversion, were observed. Replication kinetic assays in H9 cells revealed that the replication of Ala, Ser and Arg mutants was improved substantially compared with the Gly variant; the infectivity of Ala17 and Ser17 viruses was equal to, and that of Arg17 was almost equal to, the infectivity of the wild-type virus. Kinetic analysis of the cleavage of oligopeptides representing the corresponding nucleocapsid-cleavage sites revealed that all mutations improved cleavability, in good agreement with the previously proposed role of nucleocapsid cleavage in HIV-1 replication.",
author = "J. Tőzs{\'e}r and Sergey Shulenin and Young, {Matthew R.} and Briggs, {Carlton J.} and Stephen Oroszlan",
year = "2006",
month = "4",
doi = "10.1099/vir.0.81473-0",
language = "English",
volume = "87",
pages = "961--965",
journal = "Journal of General Virology",
issn = "0022-1317",
publisher = "Society for General Microbiology",
number = "4",

}

TY - JOUR

T1 - Replication-dependent fitness recovery of Human immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein

AU - Tőzsér, J.

AU - Shulenin, Sergey

AU - Young, Matthew R.

AU - Briggs, Carlton J.

AU - Oroszlan, Stephen

PY - 2006/4

Y1 - 2006/4

N2 - The genetic stability of attenuated Human immunodeficiency virus 1 (HIV-1) variants harbouring mutations (Gly or Lys) of Asn17, the protease-cleavage site of the proximal zinc finger of the nucleocapsid protein, was studied. All possible codons for the Gly mutants were tested as starting sequences. Long-term replication assays revealed that the mutants were unstable; mutations of Gly17 to Arg, Ala, Ser and Cys, as well as a Lys17Asn reversion, were observed. Replication kinetic assays in H9 cells revealed that the replication of Ala, Ser and Arg mutants was improved substantially compared with the Gly variant; the infectivity of Ala17 and Ser17 viruses was equal to, and that of Arg17 was almost equal to, the infectivity of the wild-type virus. Kinetic analysis of the cleavage of oligopeptides representing the corresponding nucleocapsid-cleavage sites revealed that all mutations improved cleavability, in good agreement with the previously proposed role of nucleocapsid cleavage in HIV-1 replication.

AB - The genetic stability of attenuated Human immunodeficiency virus 1 (HIV-1) variants harbouring mutations (Gly or Lys) of Asn17, the protease-cleavage site of the proximal zinc finger of the nucleocapsid protein, was studied. All possible codons for the Gly mutants were tested as starting sequences. Long-term replication assays revealed that the mutants were unstable; mutations of Gly17 to Arg, Ala, Ser and Cys, as well as a Lys17Asn reversion, were observed. Replication kinetic assays in H9 cells revealed that the replication of Ala, Ser and Arg mutants was improved substantially compared with the Gly variant; the infectivity of Ala17 and Ser17 viruses was equal to, and that of Arg17 was almost equal to, the infectivity of the wild-type virus. Kinetic analysis of the cleavage of oligopeptides representing the corresponding nucleocapsid-cleavage sites revealed that all mutations improved cleavability, in good agreement with the previously proposed role of nucleocapsid cleavage in HIV-1 replication.

UR - http://www.scopus.com/inward/record.url?scp=33645553646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645553646&partnerID=8YFLogxK

U2 - 10.1099/vir.0.81473-0

DO - 10.1099/vir.0.81473-0

M3 - Article

C2 - 16528046

AN - SCOPUS:33645553646

VL - 87

SP - 961

EP - 965

JO - Journal of General Virology

JF - Journal of General Virology

SN - 0022-1317

IS - 4

ER -