Functional and structural defects in HIV type 1 nef genes derived from pediatric long-term survivors

R. Geffin, D. Wolf, R. Müller, M. D. Hill, E. Stellwag, M. Freitag, G. Sass, Gwendolyn B Scott, A. S. Baur

Research output: Contribution to journalArticle

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Abstract

DNA sequences and three distinct in vitro functions of Nef were evaluated in a group of seven perinatally infected children. nef gene sequences obtained before and after virus culture showed that one of the five non-/slow progressors harbored a virus with large deletions. nef genes from the remaining four children were full length but contained discrete changes at a higher frequency than the rapid progressors. In functional studies, 40 of 44 Nef proteins derived from the whole study group were capable of binding the cellular serine kinase p62, indicating that this function is well conserved among naturally occurring viruses. In contrast, representative Nef proteins derived from the long-term non-/slow progressors were found to be defective or far less capable of enhancing viral replication and/or viral infectivity in herpesvirus saimiri-transformed human T cells and peripheral blood mononuclear cells. On reversion of highly prevalent point mutations in the defective proteins, viral replication could be restored to wild-type levels. Our results suggest that nef genes derived from pediatric long-term nonprogressors have gross deletions in isolated cases but a higher prevalence of discrete changes that may impair Nef function in primary T cell assays, but not all functions reported for Nef.

Original languageEnglish
Pages (from-to)1855-1868
Number of pages14
JournalAIDS Research and Human Retroviruses
Volume16
Issue number17
DOIs
StatePublished - Nov 20 2000

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nef Genes
nef Gene Products
Survivors
HIV-1
Pediatrics
Viruses
Saimiriine Herpesvirus 2
T-Lymphocytes
Protein-Serine-Threonine Kinases
Viral Proteins
Point Mutation
Blood Cells

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Geffin, R., Wolf, D., Müller, R., Hill, M. D., Stellwag, E., Freitag, M., ... Baur, A. S. (2000). Functional and structural defects in HIV type 1 nef genes derived from pediatric long-term survivors. AIDS Research and Human Retroviruses, 16(17), 1855-1868. https://doi.org/10.1089/08892220050195810

Functional and structural defects in HIV type 1 nef genes derived from pediatric long-term survivors. / Geffin, R.; Wolf, D.; Müller, R.; Hill, M. D.; Stellwag, E.; Freitag, M.; Sass, G.; Scott, Gwendolyn B; Baur, A. S.

In: AIDS Research and Human Retroviruses, Vol. 16, No. 17, 20.11.2000, p. 1855-1868.

Research output: Contribution to journalArticle

Geffin, R, Wolf, D, Müller, R, Hill, MD, Stellwag, E, Freitag, M, Sass, G, Scott, GB & Baur, AS 2000, 'Functional and structural defects in HIV type 1 nef genes derived from pediatric long-term survivors', AIDS Research and Human Retroviruses, vol. 16, no. 17, pp. 1855-1868. https://doi.org/10.1089/08892220050195810
Geffin, R. ; Wolf, D. ; Müller, R. ; Hill, M. D. ; Stellwag, E. ; Freitag, M. ; Sass, G. ; Scott, Gwendolyn B ; Baur, A. S. / Functional and structural defects in HIV type 1 nef genes derived from pediatric long-term survivors. In: AIDS Research and Human Retroviruses. 2000 ; Vol. 16, No. 17. pp. 1855-1868.
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