title: High IL-7 plasma levels may induce and predict the emergence of HIV-1 virulent strains in pediatric infection.
abstract: BACKGROUND
  HIV-1 infection results in severe immunodeficiency when T-cell loss cannot be compensated. IL-7 is one of the main cytokines involved in the maintenance of T-cell homeostasis. However, IL-7 can also enhance HIV-1 replication in vivo and lead to an accelerated progression of AIDS.
  
  
  OBJECTIVE
  The aim of our study was to evaluate if the increase of IL-7 levels in response to CD4+ T cell depletion could favor the emergence of HIV-1 strains with more aggressive phenotypes in pediatric infection.
  
  
  METHODS
  Plasma IL-7 levels were measured in 42 HIV-1 vertically infected infants at different times of infection, and HIV-1 isolates were obtained from primary cell cultures to determine replication rate and syncytium-inducing (SI) capability on MT-2 cell line.
  
  
  RESULTS
  IL-7 levels were significantly higher in infants harboring HIV-1 SI strains compared to those with non-syncytium-inducing (NSI) viruses (p<0.0001). Likewise, IL-7 levels were higher in infants with rapid replicating viral strains versus those with slow replicating viruses (p=0.0006). Despite the strong negative correlation between IL-7 levels and CD4+ T lymphocyte counts (r=-0.55, p=0.0001), covariance analysis demonstrated that the high levels of IL-7 were associated with more virulent phenotype features (SI and rapid replicating strains) independently of CD4+ T cell depletion. In 19 of the 42 infants, longitudinal follow-up studies showed that SI to NSI phenotype switch can occur after HAART administration, with a reduction in IL-7 levels and an increase in CD4+ T cell counts.
  
  
  CONCLUSIONS
  IL-7 response to T-cell depletion may enhance T-cell production, but at the same time may foster HIV-1 disease progression favoring the emergence of more virulent HIV-1 strains characterized by SI capability and rapid replication rate.
authors.affiliation: Laboratorio de Biología Celular y Retrovirus, Hospital Nacional de Pediatría Juan. P. Garrahan, Combate de los Pozos 1881, 1245 Buenos Aires, Argentina.
authors.forename: Julieta
authors.initials: J
authors.lastname: Kopka
authors.forename: Debora
authors.initials: D
authors.lastname: Mecikovsky
authors.forename: Paula C
authors.initials: PC
authors.lastname: Aulicino
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Mangano
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rocco
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007223:Infant; D015851:Interleukin-7 / Q000097:blood*; D007970:Leukopenia; D014774:Virulence
chemical_list: D015851:Interleukin-7