The Importance Of Interferons

Introduction

When an individual gets infected with HIV, their body’s innate immune system gets stimulated. Interferons are part of the innate immune response. They are proteins produced and released by the host cell in response to the presence of pathogens. Interferons have sensors that detect the early presence of viral transcripts and induce concerted immune response by being released by innate immune cells such as neutrophils, which leads to apoptosis.

Innate immune response towards indentifying viruses is a topic of interest. Retroviral infections are even more of a topic of discussion since there is a scares amount of information on the matter. It was once hypothesized that innate immunity had no effect on retroviruses. Due to modern science researchers are able to reveal that retroviruses in fact trigger an innate immune response. Gao et al. (2013). Researchers recently hypothesized that cGAS protein complex might be a innate sensor that can detect retroviral DNA as well as, trigger an innate immune response.

Gao et al. became aware that retroviral DNA in the cytoplasm of innate immune cells, bind to and activate cyclic guanonsine monophosphate---adenosine monophosphate synthase (cGAS) which leads to the synthesis of cyclic guanosine-adenosine monophosphate (cGAMP) from ATP and GTP. cGAMP is known to respond as a second messenger, it functions by binding and also activates the endoplasmic reticulum protein STING. Then STING activates IKB kinase (IKK) and TANK binding kinase 1 (TBK). Therefore, triggers the activation of transcription factors nuclear factor kB (NF-kB) and interferon regulatory factor 3 (IRF3). As a result these factors stimulate interferons and other cytokines in innate immunity.

Method

Many steps were ...

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Further research was done to see if HIV infection produces retroviral cDNA in the cytoplasm, if cGAS was activated when infected with HEK293T cells with HIV-GFP. In the cytosol purified cGAS proteins were prepared for ATP and GTP. The results show that cytosolic extracts from HIV infected cells did stimulate cGAS. When AZT inhibitor was used with HEK293T cells it inhibited cGAS. The results show that HIV DNA activates cGAS.

Discussion

The hypothesis that was stated by the researchers, “cGAS might detect retroviral DNA and trigger innate immune responses” it was proven according to the data and explanations provided. As discussed in class the article lacked statistical analysis and full in dept explanations and data. This was a good experiment and hopefully other researchers continue from here and perform more research and conclude better results.