Directed evolution of retrovirus envelope protein cytoplasmic tails guided by functional incorporation into lentivirus particles

Christoph A. Merten, Jörn Stitz, Gundula Braun, Eric M. Poeschla, Klaus Cichutek, Christian J. Buchholz

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In contrast to most gammaretrovirus envelope proteins (Env), the Gibbon ape leukemia virus (GaLV) Env protein does not mediate the infectivity of human immunodeficiency virus type 1 (HIV-1) particles. We made use of this observation to set up a directed evolution system by creating a library of GaLV Env variants diversified at three critical amino acids, all located around the R-peptide cleavage site within the cytoplasmic tail. This library was screened for variants that were able to functionally pseudotype HIV-1 vector particles. All selected Env variants mediated the infectivity of HIV-1 vector particles and encoded novel cytoplasmic tail motifs. They were efficiently incorporated into HIV particles, and the R peptide was processed by the HIV protease. Interestingly, in some of the selected variants, the R-peptide cleavage site had shifted closer to the C terminus. These data demonstrate a valuable approach for the engineering of chimeric viruses and vector particles.

Original languageEnglish (US)
Pages (from-to)834-840
Number of pages7
JournalJournal of Virology
Volume79
Issue number2
DOIs
StatePublished - Jan 2005

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Retroviridae Proteins
Retroviridae
Lentivirus
Gibbon ape leukemia virus
env Gene Products
HIV-1
tail
Virion
Human immunodeficiency virus 1
Gammaretrovirus
HIV Protease
peptides
proteins
pathogenicity
Libraries
HIV
Amino Acids
engineering
proteinases
R peptide

ASJC Scopus subject areas

  • Immunology

Cite this

Directed evolution of retrovirus envelope protein cytoplasmic tails guided by functional incorporation into lentivirus particles. / Merten, Christoph A.; Stitz, Jörn; Braun, Gundula; Poeschla, Eric M.; Cichutek, Klaus; Buchholz, Christian J.

In: Journal of Virology, Vol. 79, No. 2, 01.2005, p. 834-840.

Research output: Contribution to journalArticle

Merten, Christoph A. ; Stitz, Jörn ; Braun, Gundula ; Poeschla, Eric M. ; Cichutek, Klaus ; Buchholz, Christian J. / Directed evolution of retrovirus envelope protein cytoplasmic tails guided by functional incorporation into lentivirus particles. In: Journal of Virology. 2005 ; Vol. 79, No. 2. pp. 834-840.
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