The Early Interferon Alpha Subtype Response in Infant Macaques Infected Orally With SIV

Type I interferons play an important role in the early defense against viral and other pathogens. These innate responses are also critically important in shaping the subsequent adaptive response. Thus, a more thorough knowledge of innate response types and mechanisms will improve our understanding of pathogenesis and guide the development of new therapeutics. Interferon alpha (IFN-alpha) is used clinically in the treatment of HIV and hepatitis C infections. The majority of IFA-alpha therapy is based on a single IFN-alpha subtype, IFN-alpha2. However, IFN-alpha comprises a family of multiple subtypes. The biologic functions of the distinct subtypes and how they relate to disease are poorly understood. The current study developed the tools to distinguish and measure multiple IFN-alpha subtypes on the mRNA level in rhesus macaques that are used widely as an important animal model for human diseases. We were able to identify and measure nine distinct rhesus IFN-alpha subtypes. Furthermore, we could demonstrate that in response to oral pathogenic SIV infection, several IFN-alpha subtypes are rapidly induced in lymphoid but not at oral and gastrointestinal mucosal surfaces. Although each IFN-alpha subtype was induced at distinct levels, their relative expression patterns were identical in all lymphoid tissues examined.