title: Worldwide Genetic Features of HIV-1 Env α4β7 Binding Motif: The Local Dissemination Impact of the LDI Tripeptide.
abstract: BACKGROUND
  HIV-1 gp120 binds to integrin α4β7, a homing receptor of lymphocytes to gut-associated lymphoid tissues. This interaction is mediated by the LDI/V tripeptide encoded in the V2-loop. This tripeptide mimics similar motifs in mucosal addressin cellular adhesion molecule (MAdCAM) and vascular CAM (VCAM), the natural ligands of α4β7. In this study, we explored the association of V2-loop LDI/V mimotopes with transmission routes and patterns of disease progression in HIV-infected adult and pediatric patients. HIV-1 env sequences available in the Los Alamos HIV Sequence database were included in the analyses.
  
  
  METHODS
  HIV-1 V2-loop sequences generated from infected adults and infants from South and Southeast Brazil, and also retrieved from the Los Alamos database, were assessed for α4β7 binding tripeptide composition. Chi-Square/Fisher Exact test and Mann Whitney U test were used for tripeptide comparisons. Shannon entropy was assessed for conservancy of the α4β7 tripeptide mimotope.
  
  
  RESULTS
  We observed no association between the tripeptide composition or conservation and virus transmission route or disease progression. However, LDI was linked to successful epidemic dissemination of HIV-1 subtype C in South America, and further to other expanding non-B subtypes in Europe and Asia. In Africa, subtypes showing increased LDV prevalence evidenced an ongoing process of selection toward LDI expansion, an observation also extended to subtype B in the Americas and Western Europe.
  
  
  CONCLUSIONS
  The V2-loop LDI mimotope was conserved in HIV-1C from South America and other expanding subtypes across the globe, which suggests that LDI may promote successful dissemination of HIV at local geographic levels by means of increased transmission fitness.
authors.affiliation: *Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; †Programa de Oncovirologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; ‡Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil; §Laboratory of Immune Regulation, National Institutes of Health, Bethesda, MD; and ‖Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sabrina H
authors.initials: SH
authors.lastname: Hait
authors.forename: Esmeralda A
authors.initials: EA
authors.lastname: Soares
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sprinz
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Machado
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Soares
mesh_terms: D020816:Amino Acid Motifs; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D014943:Global Health; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; C514793:gp120 protein, Human immunodeficiency virus 1