title: Predominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections.
abstract: OBJECTIVE
  R5-tropic viruses are associated with HIV-1 transmission and predominate during the early stages of infection. X4-tropic populations have been detected in ~50% of patients with late-stage disease infected with subtype B viruses. In this study, we compared the frequency of X4 tropism in individuals infected with HIV-1 CRF14_BG viruses, which have a V3 loop of subtype B, with a control group of individuals infected with subtype B viruses.
  
  
  METHODS
  Sixty-three individuals infected with HIV-1 CRF14_BG (n = 31) or subtype B (n = 32) were studied. Similar proportions of newly diagnosed and chronically infected individuals were included in the subtype B and CRF14_BG groups. V3 sequences were obtained and coreceptor tropism was predicted using the Geno2pheno[coreceptor] algorithm. V3 net charge and 11/25 rules were also used for coreceptor prediction.
  
  
  RESULTS
  Overall, X4 tropism was more frequent among individuals infected with CRF14_BG viruses (87.1%) than subtype B viruses (34.3%), a difference that was statistically highly significant (P = 0.00001). Importantly, the frequencies among newly diagnosed individuals were 90% and 13.3%, respectively (P = 0.0007). Characteristic amino acids in the V3 loop (T13, M14, V19 and W20) were identified at higher frequencies in CRF14_BG viruses (54%) than subtype B viruses (0%; P < 0.000001).
  
  
  CONCLUSIONS
  CRF14_BG is the genetic form with the highest proportion of X4-tropic viruses reported to date in newly diagnosed and chronic infections. This suggests high pathogenicity for CRF14_BG viruses, potentially leading to rapid disease progression. CCR5 antagonists will be ineffective in most CRF14_BG-infected patients, even at early stages of infection.
authors.affiliation: HIV Biology and Variability Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Pérez-Álvarez
authors.forename: Elena
authors.initials: E
authors.lastname: Delgado
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vega
authors.forename: Vanessa
authors.initials: V
authors.lastname: Montero
authors.forename: Teresa
authors.initials: T
authors.lastname: Cuevas
authors.forename: Aurora
authors.initials: A
authors.lastname: Fernández-García
authors.forename: Beatriz
authors.initials: B
authors.lastname: García-Riart
authors.forename: Sonia
authors.initials: S
authors.lastname: Pérez-Castro
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodríguez-Real
authors.forename: María José
authors.initials: MJ
authors.lastname: López-Álvarez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernández-Rodríguez
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Lezaun
authors.forename: Patricia
authors.initials: P
authors.lastname: Ordóñez
authors.forename: Carmen
authors.initials: C
authors.lastname: Ramos
authors.forename: Elena
authors.initials: E
authors.lastname: Bereciartua
authors.forename: Sara
authors.initials: S
authors.lastname: Calleja
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sánchez-García
authors.forename: Michael M
authors.initials: MM
authors.lastname: Thomson
mesh_terms: D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D056189:Viral Tropism
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D015728:Receptors, HIV
keywords: HIV; antiretroviral therapy; coreceptors