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.

STUDY DESIGN:

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: Julieta Kopka, Debora Mecikovsky, Paula C Aulicino, Andrea M Mangano, Carlos A Rocco, Rosa Bologna, Luisa Sen
• Journal: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology (J Clin Virol) Vol. 33 Issue 3 Pg. 237-42 (Jul 2005) ISSN: 1386-6532 [Print] Netherlands
• PMID: 15911446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-7

Topics

• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (immunology)
• Child
• Child, Preschool
• HIV Infections (immunology, virology)
• HIV-1 (classification, genetics, pathogenicity)
• Humans
• Infant
• Interleukin-7 (blood)
• Leukopenia
• Virulence