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How Genes React Differently to HIV-1 and HIV-2


 

When HIV encounters a host cell, its success in infecting the cell and in overall disease progression is dependent on a multitude of factors related to how the host cell expresses certain genes.

The authors of a paper published Jan. 28 in PLOS One wanted to know how gene expressions differ between HIV-1 and HIV-2 infection. HIV-2 infection is exceedingly rare in the United States. Although HIV-1 and HIV-2 have the same modes of transmission and can cause AIDS, HIV-2 is characterized by its subjects having much lower viral loads and much higher T-cell counts, even in the presence of an AIDS-defining illness.

Researchers from George Mason University wanted to better understand how the two viruses work and which biomarkers may be responsible for HIV-2 being less lethal. “Understanding the differential regulation of host cellular factors in response to HIV-1 and HIV-2 infections will help us to understand the apparent differences in rates of disease progression and pathogenesis,” the authors wrote in the abstract. “This knowledge would aid in the discovery of new biomarkers that may serve as novel targets for therapy and diagnosis.”

Using a tool called the Agilent Whole Human Genome Oligo Microarray, the researchers were able to see that hosts reacted much more intensely with HIV-1 in terms of gene expression than with HIV-2. “We analyzed the effects of HIV-1 (MN) and HIV-2 (ROD) infection on the expression of host factors in PBMC (T cells, B cells and NK cells) at the RNA level,” the researchers reported. “Gene expression profiling analysis identified a subset of differentially expressed genes in HIV-1 and HIV-2 infected cells. Genes involved in cellular metabolism, apoptosis (cell death), immune cell proliferation and activation cytokines, chemokines and transcription factors (replication) were differentially expressed in HIV-1 infected cells. Relatively few genes were differentially expressed in cells infected with HIV-2.”

The specific findings make for very heavy reading, but if you are so inclined you can read the entire paper by clicking here.

HIV works by injecting its own DNA into a cell and “hijacking” it to replicate and wreak havoc throughout the body. This experiment gave researchers a way to examine more intimately than ever before how a host cell’s genes react to this process.

“This is a significant step toward the identification of a set of biomarkers based on host genomic foot prints that may become powerful tools in defining the pathogenesis of diverse HIV variants, especially when coupled with classic markers, such as CD4+ T cell count and viral load,” the researchers concluded. “Finally, identification of the differences in specific host metabolic and biosynthetic pathways impacted by HIV-1 or HIV-2 infection may lead to the use of more effective and targeted therapies for each of these HIV types than currently available.”