Unique Acquisition of Cytotoxic T-Lymphocyte Escape Mutants in Infant Human Immunodeficiency Virus Type 1 Infection

Abstract

The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections.

HLA-Cw*03-Restricted CD8+T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation

“…Also, these data suggest that Gag-303-V is selected in the setting of a weak immune response and consistent with the narrower immune response that is typically observed in pediatric infection or in adults with more advanced disease (39). Escape has also been described previously in the child, but not the mother, of a mother-child pair where the HLA alleles and the response were shared (29). Our results illustrate the fine balance that exists between opposing selection forces and the fact that this balance may shift during the course of infection within a single individual as disease progresses, as well as differing between individuals.…”

Cytotoxic T-Lymphocyte Escape Mutations Identified by HLA Association Favor Those Which Escape and Revert Rapidly

“…Patients were included in the study only if their CD4 counts were above 300 cells per mm 3 at the time of enrollment and if they had been on continuous antiretroviral therapy (ART) with a plasma viral load of less than 50 copies per ml for at least 6 months. Although these patients were followed for an average of 14 months, for the present study, only data from a sample taken toward the end of the study (i.e., while the patients remained off treatment) were (18,19,24,28,37). For each mutation, the average time between infection and escape in HLA-matched hosts (the reciprocal of the escape rate) and the average time between infection and reversion in HLAmismatched hosts are provided.…”

“…Mutations at each of these sites have previously been shown to confer escape in vitro (18,19,24,28,37). The rates at which they escape in HLA-matched hosts and revert in HLA-mismatched hosts, as measured from a longitudinal cohort of 189 acute seroconverters, are presented in Table 1.…”

Immunité maternelle et transmission mère-enfant du VIH et du VHC

“…On a observé depuis longtemps que la TME est associée à une charge virale maternelle élevée -le meilleur facteur prédictif du risque de transmission -et à un faible décompte de cellules T CD4 + , deux robustes indicateurs d'immunodéficience : plus la maladie progresse, plus le décompte CD4 diminue et plus le risque de TME augmente [20]. Comparées aux mères qui ne transmettent pas le virus, les activités cytotoxiques et suppressives des lymphocytes T CD8 + anti-VIH sont réduites chez les mères qui le transmettent [21], bien que les variants VIH qui sont préférentiellement transmis à l'enfant soient ceux-là même qui échappent à la réponse cellulaire maternelle [22] et aux anticorps neutralisants [23]. On pense également que des facteurs génétiques associés à la réponse immunitaire, notamment la présence de l'allèle HLA-DR13, ainsi que la discordance entre les HLA de classe I de la mère et du foetus protègeraient ce dernier contre la TME du VIH [24].…”