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

被引:51
作者
Geffin, R
Wolf, D
Müller, R
Hill, MD
Stellwag, E
Freitag, M
Sass, G
Scott, GB
Baur, AS [1 ]
机构
[1] Univ Miami, Sch Med, Dept Pediat, Miami, FL 33136 USA
[2] Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-91054 Erlangen, Germany
[3] Nova SE Univ, Ft Lauderdale, FL 33328 USA
关键词
D O I
10.1089/08892220050195810
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1855 / 1868
页数:14
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