Dataset Information

The early interferon alpha subtype response in infant macaques infected orally with SIV.

ABSTRACT: 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.

SUBMITTER: Easlick J

PROVIDER: S-EPMC2927738 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The early interferon alpha subtype response in infant macaques infected orally with SIV.

Easlick Juliet J Szubin Richard R Lantz Samantha S Baumgarth Nicole N Abel Kristina K

Journal of acquired immune deficiency syndromes (1999) 20100901 1

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 b ...[more]

PMID: 20616742

Similar Datasets

Project description:Globally, 1.8 million children are living with HIV-1. While antiretroviral therapy (ART) has improved disease outcomes, it does not eliminate the latent HIV-1 reservoir. Interventions to delay or prevent viral rebound in the absence of ART would be highly beneficial for HIV-1-infected children who now must remain on daily ART throughout their lifespan. Here, we evaluated therapeutic Ad48-SIV prime, MVA-SIV boost immunization in combination with the TLR-7 agonist GS-986 in rhesus macaque (RM) infants orally infected with SIVmac251 at 4 weeks of age and treated with a triple ART regimen beginning 4 weeks after infection. We hypothesized immunization would enhance SIV-specific T cell responses during ART-mediated suppression of viremia. Compared to controls, vaccinated infants had greater magnitude SIV-specific T cell responses (mean of 3475 vs 69 IFN-γ spot forming cells (SFC) per 106 PBMCs, respectively, P = 0.01) with enhanced breadth of epitope recognition and increased CD8+ and CD4+ T cell polyfunctionality (P = 0.004 and P = 0.005, respectively). Additionally, SIV-specific gp120 antibodies against challenge and vaccine virus strains were significantly elevated following MVA boost (P = 0.02 and P < 0.001, respectively). GS-986 led to expected immune stimulation demonstrated by activation of monocytes and T cells 24 hours post-dose. Despite the vaccine-induced immune responses, levels of SIV DNA in peripheral and lymph node CD4+ T cells were not significantly different from controls and a similar time to viral rebound and viral load set point were observed following ART interruption in both groups. We demonstrate infant RMs mount a robust immunological response to this immunization, but vaccination alone was not sufficient to impact viral reservoir size or modulate rebound dynamics following ART release. Our findings hold promise for therapeutic vaccination as a part of a combination cure approach in children and highlight the importance of a pediatric model to evaluate HIV-1 cure interventions in this unique setting of immune development.

Dataset Information

The early interferon alpha subtype response in infant macaques infected orally with SIV.

Publications

The early interferon alpha subtype response in infant macaques infected orally with SIV.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets