HCV adaptations to altered CD8+ T-cell immunity during pregnancy.

Abstract

Robust, polyfunctional CD8+ T-cell responses targeted to multiple viral epitopes have been associated with successful resolution of acute HCV infection. In most individuals, however, immunity fails and chronic viremia ensues as CD8+ T cells become functionally exhausted or select viral variants with escape mutations in class I epitopes. During pregnancy, dysfunctional HCV-specific CD8+ T-cell responses may be further impaired by maternal–fetal tolerance processes such as the expansion of regulatory T-cell populations or hormonal changes. Recent evidence suggests that HCV adapts to relaxed maternal CD8+ T-cell pressure in pregnancy by shedding unfit escape mutations in certain class I epitopes, resulting in the selection of viruses with more efficient replication. Emergence of HCV variants with enhanced replicative capacity during pregnancy has ramifications for mother-to-child transmission, the primary route of HCV infection in children, and could potentially be relevant to other important, vertically transmissible, persistent viruses such as HBV and HIV. HCV has infected over 185 million people worldwide and persists in approximately 75% of these individuals, predisposing to liver inflammation, cirrhosis and hepatocellular carcinoma [1]. More than 1 million children are born to HCV-infected mothers each year, and 3–5% acquire the infection in utero or at delivery, making vertical transmission the leading route of pediatric HCV infection in the developed world [2]. Here, we review the critical role of CD8+ T-cell immunity in HCV infection, its modulation in pregnancy and recent evidence that HCV takes advantage of the unique immunologic niche of pregnancy to improve replicative fitness and potentially promote vertical transmission.