High IL-7 plasma levels may induce and predict the emergence of HIV-1 virulent strains in pediatric infection.
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.
Kopka
Julieta
J
Laboratorio de Biología Celular y Retrovirus, Hospital Nacional de Pediatría Juan. P. Garrahan, Combate de los Pozos 1881, 1245 Buenos Aires, Argentina.
Mecikovsky
Debora
D
Aulicino
Paula C
PC
Mangano
Andrea M
AM
Rocco
Carlos A
CA
Bologna
Rosa
R
Sen
Luisa
L
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
D015851:Interleukin-7