Partial "repair" of defective NEF genes in a long-term nonprogressor with human immunodeficiency virus type 1 infection

A 36-bp deletion close to the 5' end of NEF that impaired Nef function was found in a long-term nonprogressor with human immunodeficiency virus type 1 (HIV-1) infection, Forms containing an adjacent duplication of 33 bp were also frequently observed. The duplication showed no homology to the deleted region but restored the overall length of the first variable loop of Nef. NEF alleles carrying the duplication were active in class I major histocomp atibility complex (MHC-I) down-modulation and enhancement of virus infectiv ity, However, they showed little activity in CD4 down-regulation and were u nable to stimulate viral replication in human peripheral blood mononuclear cells. Our study indicates that the enhancement of virion infectivity and t he stimulation of HIV-1 replication in lymphocytes are distinct functions o f Nef, Our Endings also illustrate the capacity for repair of attenuating d eletions in HIV-1 infection and suggest that a selective pressure for Nef-m ediated MHC-I down-modulation and/or enhancement of virion infectivity exis ts.