Genetic Determinants of Pediatric HIV-1 Infection: Vertical Transmission and Disease Progression Among Children

Claudine Matte,Michel Roger

doi:10.1007/bf03401864

Abstract

It is very likely that perinatal human immunodeficiency virus type 1 (HIV-1) infection is influenced by a combination of virologic and host factors. A greater understanding of the role played by various risk factors for HIV-1 infection is crucial for the design of new preventive and therapeutic strategies. In recent years, a number of studies have suggested that host genetic factors are important determinants of both the susceptibility to perinatal HIV-1 infection and the subsequent pathogenesis of acquired immunodeficiency syndrome (AIDS). Control of HIV-1 infection involves the processing of specific viral peptides and their presentation to cells of the immune system by highly polymorphic human leukocyte antigen (HLA) alleles. The contribution of multiple HLA class I and II alleles in modulating pediatric HIV/AIDS outcomes has now been confirmed by several independent groups. Penetration of HIV-1 into cells is mediated by interaction between CD4 and chemokine receptors that serve as entry coreceptors. Genetic polymorphisms in chemokine ligand and chemokine receptor genes have recently been associated both with mother-to-child HIV-1 transmission and disease progression in children. These observations suggest a key role for genetic factors in pediatric HIV-1 infection. This article describes the current state of knowledge regarding host genetic influences on pediatric HIV-1 infection and discusses the role of these genes in HIV/AIDS pathogenesis.

Highlights

UNAIDS and the World Health Organization (WHO) estimated that 15.7 million women, most of whom are of childbearing age, were living with human immunodeficiency virus (HIV) at the end of 1999 [1]
Recent studies have demonstrated that most vertical transmission occurs with macrophage-tropic or NSI viral isolates [15,51] and that progression to acquired immunodeficiency syndrome (AIDS) occurs more rapidly in infants with NSI strains [14], suggesting that the polymorphism of CCR5 might influence pediatric human immunodeficiency virus type 1 (HIV-1) infection
HIV-1 transmission in utero may take place by a process that is more dependent on human leukocyte antigen (HLA) molecules than chemokine receptor expressions, compared with transmission that occurs at or after birth

Summary

Introduction

UNAIDS and the World Health Organization (WHO) estimated that 15.7 million women, most of whom are of childbearing age, were living with human immunodeficiency virus (HIV) at the end of 1999 [1]. This review will focus on the role of human leukocyte antigen (HLA), chemokine receptors, and stromal-derived factor-1 (SDF1) genes on perinatal HIV-1 transmission and disease progression to AIDS. Roger: Genetic Determinants of Pediatric HIV-1 Infection 585 age and decreased risk of clinical manifestations were associated with HLA DPB1 alleles (DPB1*0101, *0301).

Results

Conclusion