Influence of Nef, an HIV accessory protein, on viral immunopathogenesis

CORRÓ, GUILLERMO; DE MAIO, FEDERICO ANDRÉS; ROCCO, CARLOS; AULICINO, PAULA; MANGANO, ANDREA; SEN, LUISA

Río de Janeiro

Congreso; XIII International Congress of Immunology; 2007

International Immunology Society (IIS)

Immune system failure is the major feature in the advanced HIV-1 infection, marked by systematic T cell depletion. The asymptomatic period range from months to more than 15 years, depending on multiple viral and cellular factors. The viral accessory protein, Nef, which has been found in plasma from infected patients, has cytotoxic effect on CD4+ T cells in vitro and can inhibit specific antibodies secretion by B lymphocytes. Therefore, Nef may be an important viral factor that influence on infection evolution and disease development. Our aim is to establish the role of HIV-1 nef gene on viral immunopathogenesis in vertical infected children from Argentina. We studied 10 patients considered as LTNP (long-term non-progressor: 10 years of infection without AIDS and at least 100 months without ARV therapy), 10 patients as RP (rapid progressor: AIDS before 2 years of infection) and 3 as Discordant patients (D): persistent high viral loads and CD4+ counts. The nef gene was amplified from peripheral blood mononuclear cells provirus by nested PCR and sequenced afterwards. LTNPs exhibited abnormal nef amplicons lengths and in some cases more than one fragment. Furthermore, sequence abnormalities were found in some LTNPs (prematures stop codons due to not-in-frame deletions) and Ds (lack of 5´end), while no length or sequence abnormalities were found in studied RP. Our results support the concept that a virus carrying an abnormal nef gene can be less aggressive for host immune system. Therefore, Nef could be a relevant factor implied on progression to AIDS.