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Sex hormones modulated HIV pathogenesis
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SEATTLE — Sex hormones appear to modulate HIV pathogenesis through upregulation of cellular inflammatory chemokines, according to researchers from the Center for Biologics Evaluation and Research at the FDA.
These chemokines may play a role in increased HIV acquisition by women with herpes simplex virus type 2 (HSV-2) who are using hormonal contraceptives, they said.
The researchers infected CEM-SS cells with HIV-1 and/or HSV-2. The coinfection was performed either with HIV-1 infection first or HSV-2 virus first. Similar experiments were performed with sex steroid hormones, including estrogen, progesterone and testosterone added to the virus infections.
Virus titer was measured 7 days after infection using a multiplex TaqMan assay. Also, a gene expression analysis was performed for inflammatory cytokines and receptors 7 days after infection.
The addition of sex hormones upregulated HIV-1 and HSV-2 viral DNA. For HIV-1, it was upregulated 5,000 pg to 10,000 pg of DNA per milliliter, and for HSV-2, it was upregulated to 250 pg to 400 pg of DNA. This is about a 20-fold increase compared with cells that did not receive hormones.
In coinfected cells that were treated with estrogen and progesterone, there were significant increases of more than 1,000 pg of HIV-1 DNA when the cells were infected first with HSV-2 then with HIV-1. After gene expression profiling, CXCL14 and TOLLIP were found to be upregulated 30- to 60-fold, for increased HIV replication in the coinfected cells that were treated with estrogen and progesterone.
For more information:
- Ragupathy V. #221. Presented at: 19th Conference on Retroviruses and Opportunistic Infections; March 3-8, 2012; Seattle.
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