Functional and Structural Defects in HIV Type 1nefGenes Derived from Pediatric Long-Term Survivors
| Autor: | Gabi Sass, Andreas Baur, Dietlinde Wolf, Rüdiger Müller, Martin D. Hill, Rebeca Geffin, Martina Freitag, Gwendolyn B. Scott, Elisabeth Stellwag |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adolescent
viruses Molecular Sequence Data Immunology HIV Infections Protein Serine-Threonine Kinases Biology Virus Replication medicine.disease_cause Gene Products nef Herpesviridae Virus HIV Long-Term Survivors Virology medicine Humans Point Mutation Gammaherpesvirinae Amino Acid Sequence nef Gene Products Human Immunodeficiency Virus Child Gene Phylogeny Genetics Viral culture Point mutation Genetic Variation Infant Sequence Analysis DNA biology.organism_classification Genes nef Infectious Diseases p21-Activated Kinases Viral replication Lentivirus HIV-1 Sequence Alignment Gene Deletion |
| Zdroj: | AIDS Research and Human Retroviruses. 16:1855-1868 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/08892220050195810 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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