Biomedical subjects

Thillagavathie Pillay

Publications and source records attributed to Thillagavathie Pillay.

3 recordsLinked to original sources

PubMed2005

Adaptive evolution in perinatal HIV-1.

The immune-viral dynamics of the transmission of HIV-1 from mother to child are poorly understood, despite 20 years of research. Here we review evidence that the maternal immune response against HIV-1 can select forms of the virus that evade immunity and when transmitted have negative consequences in the child. Moreover, recent studies indicate that when wild-type virus is transmitted, an early immune response in the child can lead to the selection of viral escape forms in the first few months of life. These data suggest that adaptive immune surveillance in both mother and child contributes to the pathogenesis of early perinatal HIV-1. These observations augment our general understanding of the processes that determine the evolution of HIV-1 as it passes from one host to another.

Biological Evolution↗

PubMed2005

Unique acquisition of cytotoxic T-lymphocyte escape mutants in infant human immunodeficiency virus type 1 infection.

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.

Amino Acid Sequence↗

PubMed2004

CD8 epitope escape and reversion in acute HCV infection.

In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.

Acute Disease↗