Researchers at the 48th IDSA Meeting Find a Correlation Between p21 Expression and HIV Production in CD4+ T Cells
Vancouver, Canada, 48th Annual Meeting of the Infectious Diseases Society of America, 22 OCT. 2010
Mathias Lichterfeld, MD, PhD, from the Infectious Diseases Division at Massachusetts General Hospital, showed his research study focusing on HIV replication in CD4 T cells from elite controllers (n = 15), from HIV-1 negative individuals (n = 14), from individuals with progressive HIV-1 disease (n = 16), and from infected patients treated with highly active antiretroviral therapy (HAART) (n = 10).
The cells were analyzed after ex vivo infection with an HIV-1 viral vector or primary isolates to quantify extra- and intrachromosomal HIV-1 DNA and messenger (m)RNA. Expression of the p21 gene was quantified in quiescent and activated CD4 T cells from elite controllers and from the reference populations.
p21 is a host protein originally described as a product of a tumor suppressor gene.
Dr. Lichterfeld reported that these cells from elite controllers were significantly less susceptible to infection with HIV-1 than cells from the reference populations. The less efficient viral replication in the cells of elite controllers was associated with a 10- to 20-fold higher expression of p21 than in the cells of the reference populations. Using an ex vivo HIV-1 infection assay, Dr. Lichterfeld showed that chemical blockade of p21 enhanced reverse transcription and viral mRNA transcription in CD4 cells. In elite controllers, p21 is about 10- to 100-fold higher than in other patients.
t's not a complete resistance. Cells still can be infected, but the susceptibility is very reduced. These results are particularly interesting in order to understand the mechanisms involved in the maintenance of HIV persistence.
Infectious Diseases Society of America (IDSA) 48th Annual Meeting: Abstract 88.
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Key words: expression, hiv, p21, reservoir, reservoirs