Identification of a cluster of HIV-1 controllers infected with low replicating viruses

PLoS One. 2013 Oct 30;8(10):e77663. doi: 10.1371/journal.pone.0077663. eCollection 2013.

Abstract

Long term non-progressor patients (LTNPs) are characterized by the natural control of HIV-1 infection. This control is related to host genetic, immunological and virological factors. In this work, phylogenetic analysis of the proviral nucleotide sequences in env gene from a Spanish HIV-1 LTNPs cohort identified a cluster of 6 HIV-1 controllers infected with closely-related viruses. The patients of the cluster showed common clinical and epidemiological features: drug user practices, infection in the same city (Madrid, Spain) and at the same time (late 70's-early 80's). All cluster patients displayed distinct host alleles associated with HIV control. Analysis of the virus envelope nucleotide sequences showed ancestral characteristic, lack of evolution and presence of rare amino-acids. Biological characterization of recombinant viruses with the envelope proteins from the cluster viruses showed very low replicative capacity in TZMbl and U87-CD4/CCR5 cells. The lack of clinical progression in the viral cluster patients with distinct combinations of protective host genotypes, but infected by low replicating viruses, indicate the important role of the virus in the non-progressor phenotype in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Disease Progression
  • Female
  • Genes, env / genetics
  • HIV Infections / genetics*
  • HIV Long-Term Survivors
  • HIV-1 / genetics*
  • Humans
  • Male
  • Phylogeny
  • Spain
  • Virus Replication / genetics*
  • env Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • env Gene Products, Human Immunodeficiency Virus

Grant support

Work in CNM is supported by grants [SAF 2007-61036 and 2010-17226] from MICINN Spain, by grants [36558/06, 36641/07, 36779/08, 360766/09] from Fundación para la investigación y prevención del SIDA en España (FIPSE) Spain, and in part by the RETIC de Investigación en SIDA [RD06/006/0036] of the Fondo de Investigaciones Sanitarias (FISss). Work in H12 de Octubre was financed by FIPSE [36749], and ISCIII-FIS [PI080806 and PI1101580] to RD. The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by the Instituto de Salud Carlos III, Spanish Health Department (Grant n° RD06/006/0035) and FIPSE. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.