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Abstract: 3110

A22 - Viral and host factors in long-term non


progressors
12 A22
Longitudinal characterization of a nef-LTR deleted HIV in a long term non-progressor

J.A. Vázquez-Pérez, S. Avila-Rios, K.J. Torres, E. Sevilla-Reyes, G. Reyes-Terán


Instituto Nacional de Enfermedades Respiratorias, Centro de Investigación en Enfermedades Infecciosas, Mexico City, Mexico

Background: Several mechanisms have been associated with the lack of progression in HIV disease, including immunological,
genetical and virological factors. Few reports have described infections with attenuated-HIV strains in some long-term non-
progressors, such as a work in the Syndey Blood Bank Cohort, characterizing six individuals infected with a nef-LTR defective-
HIV through blood transfusion. Further addressing the importance of such virological mechanisms in HIV attenuation could lead
to the development of strategies to lower HIV virulence.
Methods: We characterized a nef-defective virus in a Mexican LTNP after 8 years of infection (consistently CD4+ T cell counts
>500 cells/ul and viral loads <3000 copies/mL). The nef-LTR region was amplified from viral RNA and PBMC genomic DNA by
nested PCR. Nucleotide sequences of PCR products and independent clones were sequenced, aligned and analyzed with
Clustal X and MEGA 4.0. Other factors associated with non-progression such as the CCR5 Δ32 deletion or protective HLA
alleles were discarded.
Results: An analysis spanning an 8-year-infection period demonstrated a progressive loss of nef sequence from the early
sequences (432 nucleotides) vs the most recent sequences studied (363 nucleotides). None of these viruses were predicted to
translate a complete Nef protein because a variety of deletions around amino acid 75 introduced in-phase termination codons
at amino acid positions 81 or 116. None of the viruses presented a complete PXXP region, which has been shown to be
essential for several Nef functions. Deletions in both NFAT binding sites were also observed.
Conclusions: Our studies confirm the importance of the nef gene in HIV pathogenesis and support previous observations
regarding the contribution of nef deletions to non-progression.

Country(ies) of Research: Mexico


Presenter: Mr. PhD Joel Armando Vázquez-Pérez, Instituto Nacional de Enfermedades Respiratorias, Mexico City
[Mexico]