Jinmin Ma:
The Immune Molecular Characteristic Research in the Development of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome in AIDS Patient

Date: 28-02-2018    Supervisor: Karsten Kristiansen

Human immunodeficiency virus-1 (HIV-1) is a retrovirus that primarily infects components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. HIV directly and indirectly destroys CD4+ T cells, which leads to severe immunodeficiency and enhanced susceptibility to opportunistic infections in most infected patients.

Highly active antiretroviral treatment (HAART) is able to suppress viral replication, lower the amount of virus (viral load) in a patient’s body, and partially restore circulating CD4+ T cells so that the immune system is better able to deal with HIV-1 infections. However, the accumulative side effects or problems have emerged with ART in patients. The increasing number of patients with issues of drug toxicity, emergence of drug resistant viruses, immune reconstitution inflammatory syndrome (IRIS) following the initiation of HAART and unable to normalize immune activation in HIV-infected individuals posed new challenges to the fight against AIDS. Furthermore, Tuberculosis (TB) is still one of the world’s greatest public health threats. Combined with HIV, the two diseases can be much more devastating. TB infection is the most common opportunistic infection in the HIV/AIDS positive patients, and the proportion reaches 30%~60%, even more, nearly 50%-80% HIV/AIDS patients die because of TB infecting. Highly Active Antiretroviral Therapy (HAART) is a useful method for therapy these patients, but Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication of HAART in HIV-TB co-infected patients. However, the disease mechanism is poorly understood, prognosis of TB-IRIS is currently impossible, and diagnosis is highly challenging.

Genome-wide gene expression profiling is an informative method used to reveal global changes of the immune system in health and disease, and has been particularly useful in identifying biomarkers, examining the disease states, and investigating immune responses. Although a number of transcriptome studies in HIV infection have been conducted, most of them based on conventional microarray technologies that focused on a limited number of genes. Recently, Next-generation sequencing (NGS) technology has provided a new method for both mapping and quantifying transcriptomes. This method, termed RNA-Seq (RNA sequencing), provides highly accurate measurements of genome-wide gene expression through high-throughput DNA sequencing and generates high quality transcriptome data, including transcript abundance, gene structure, alternative splicing, profiles of non-coding RNA species and genetic polymorphisms. Such data may provide a more complete and comprehensive understanding of HIV pathogenesis.