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.
Highlights
Long term non-progressor patients (LTNPs) are individuals infected with HIV-1 for more than 10 years, maintaining high CD4+ lymphocytes numbers without clinical symptoms in absence of therapy [1]
The global and quasispecies nucleotide sequences from a cohort of Spanish LTNPs and chronic patients, obtained between 1989 and 2005, were analyzed by Maximum Likelihood (ML) in the gp120 C2-V5 region in env gene (Figure S1). This analysis showed that all nucleotide sequences obtained in different time points from each patient formed monophyletic clades, except sequences from 6 individuals. These sequences could not be segregated per patient, and they formed a phylogenetic cluster with short branch lengths and very low mean genetic distances among sequences (1.1%) samples were recovered during 16 years (1989–2005)
All patients included in the cluster had intravenous drug practices (IDU) in the late 70’s and early 80’s; they lived in Madrid and had a first HIV-1 positive serology between1985 and 1990 (Table 1)
Summary
Long term non-progressor patients (LTNPs) are individuals infected with HIV-1 for more than 10 years, maintaining high CD4+ lymphocytes numbers without clinical symptoms in absence of therapy [1]. Immunological and virologic factors have been investigated in relation to the natural control in HIV-1 LTNPs. Control of viral replication was associated with the presence of certain human leukocyte antigen (HLA) class I alleles, in the HLA-B locus like the HLA-B57/B27 haplotypes with a significantly higher frequency in HIV-1 controller cohorts [3,4]. Qualitative attributes of innate and adaptive immune response was associated with viral control of HIV-1 infection [9,10]. In this control, the importance of antigen sensitivity and T-cell receptor avidity were reported [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
