title: HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of immunological failure in infected children.
abstract: BACKGROUND
  HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5(broad) viruses), was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT) of HIV-1 and pediatric disease progression.
  
  
  RESULTS
  Viral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting) and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5(narrow) phenotype (n = 20), but R5(broad) and R5X4 viruses were also found in seven and one case, respectively. The presence of R5(broad) and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3) or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5(broad) phenotype, however, the presence of the R5(broad) virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad) viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5(broad) phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant.
  
  
  CONCLUSIONS
  Our results show that R5(broad) viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5(narrow) phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.
authors.affiliation: Viral Evolution and Transmission Unit, DIBIT, Fondazione Centro San Raffaele, Milan, Italy. cavarelli.mariangela@hsr.it
authors.forename: Mariangela
authors.initials: M
authors.lastname: Cavarelli
authors.forename: Ingrid
authors.initials: I
authors.lastname: Karlsson
authors.forename: Marisa
authors.initials: M
authors.lastname: Zanchetta
authors.forename: Liselotte
authors.initials: L
authors.lastname: Antonsson
authors.forename: Anna
authors.initials: A
authors.lastname: Plebani
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Fenyö
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Scarlatti
mesh_terms: D015704:CD4 Antigens / Q000096:biosynthesis; D018925:Chemokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000821:virology; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D010641:Phenotype; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000235:genetics; D019713:Receptors, CCR5 / Q000378:metabolism / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D018925:Chemokines; D019713:Receptors, CCR5; D019718:Receptors, CXCR4