Nef gene defects identified in paediatric long-term HIV survivors

Investigators have identified functional and structural nef gene defects that occur in HIV-infected paediatric patients with a non- or slow- progressing form of the disease, according to a report published in the November 20th issue of AIDS Research and Human Retroviruses. Dr. Rebeca Geffin, from the University of Miami School of Medicine, and colleagues analysed the structure and function of HIV-1 nef genes in seven children who were perinatally infected with the virus. Of this group, four patients were long-term nonprogressors, one was a slow progressor, and two were rapid progressors. Of the five slow progressors or nonprogressors, only one patient had large deletions of the nef gene, the authors note. The other four had nef genes of normal size but with a higher frequency of discrete changes than the genes of rapid progressors.

On functional analysis, the majority of Nef proteins derived from the study group were “capable of binding…kinase p62, indicating that this function is well conserved among naturally occurring viruses,” the researchers note. However, compared with rapid progressors, Nef proteins from slow or nonprogressors were much less effective at promoting viral replication or infectivity when tested in various assays. The authors also found that reversing the highly prevalent point mutations in the defective Nef proteins restored the viral replication ability to wild-type levels.

“Our data imply that some but not all Nef functions may be defective in nef alleles from paediatric long-term nonprogressors,” the researchers explain. “Despite looking at representative changes characteristic of Nef proteins in individual children, our results could be coincidental and statistically nonsignificant.” However, it is possible that these changes do, in fact, have an impact on disease progression, Dr. Geffin’s team concludes.