The role of serpin and cystatin antiproteases in mucosal innate immunity and their defense against HIV

Am J Reprod Immunol. 2014 Jan;71(1):12-23. doi: 10.1111/aji.12166. Epub 2013 Oct 31.

Abstract

Antiproteases play diverse roles in nature, from regulating protease activity to innate defense against microorganisms. Recently, antiproteases have been shown to play important roles in HIV pathogenesis including, inhibiting HIV binding and replication and reducing activation and inflammation of susceptible cells. They have also been implicated as one of the initial host responders, in plasma, to control replication of HIV. More recently, antiproteases expressed at the mucosal surface have been linked to reduced susceptibility to HIV infection in HIV-exposed sero-negative individuals. These factors are expressed in the epithelial layer of the female genital tract, thus at the frontline of defense against mucosal infection. This review focuses on the specific antimicrobial roles of antiproteases, focusing on serpins and cystatins, with an emphasis on their known and potential roles in HIV infection. Their potential as therapeutic interventions to combat HIV is also discussed.

Keywords: Cystatins; HIV; female genital tract; innate mucosal immunity; serpins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / metabolism*
  • Cystatins / metabolism*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Female
  • Genitalia, Female / immunology
  • Genitalia, Female / virology
  • HIV / physiology*
  • HIV Infections / immunology*
  • Humans
  • Immunity, Innate
  • Mucous Membrane / immunology*
  • Mucous Membrane / virology
  • Protease Inhibitors / metabolism*
  • Serpins / metabolism*
  • Virus Replication

Substances

  • Antiviral Agents
  • Cystatins
  • Protease Inhibitors
  • Serpins