Estradiol and Progesterone Regulate HIV Type 1 Replication in Peripheral Blood Cells
| Autor: | Susana N. Asin, Alexandra L. Howell, Alysha M. Heimberg, Christiane Rollenhagen, Susan K. Eszterhas |
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| Rok vydání: | 2008 |
| Předmět: |
Gene Expression Regulation
Viral Male medicine.medical_specialty Transcription Genetic medicine.medical_treatment Immunology HIV Infections Endogeny Virus Replication Peripheral blood mononuclear cell Blood cell Sex hormone-binding globulin Virology Internal medicine medicine Humans Cells Cultured Progesterone HIV Long Terminal Repeat Estradiol biology Infectious Diseases medicine.anatomical_structure Endocrinology Cytokine Viral replication Chemokine secretion HIV-1 Leukocytes Mononuclear biology.protein Female Hormone |
| Zdroj: | AIDS Research and Human Retroviruses. 24:701-716 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2007.0108 |
| Popis: | Endogenous levels of estradiol and progesterone fluctuate in the peripheral blood of premenopausal women during the reproductive cycle. We studied the effects of these sex hormones on HIV-1 replication in peripheral blood mononuclear cells (PBMCs). We compared HIV-1 replication in PBMCs infected in the presence of mid-secretory (high concentrations) and mid-proliferative (low concentrations) or in the absence of sex hormones. With PBMCs from men, we used concentrations of estradiol and progesterone that are normally present in their plasma. Our findings demonstrate that mid-proliferative phase conditions increased, and mid-secretory phase conditions decreased, HIV-1 replication. To determine if sex hormones affect specific stages of the viral life cycle we performed real-time PCR assays and found decreased levels of HIV-1 integration in the mid-secretory phase and increased levels viral transcription in the mid-proliferative phase. No significant effects on HIV-1 reverse transcription or on CCR5 expression were found. In addition, we assessed hormonal regulation of the HIV-1 LTR in the absence of the viral regulatory protein Tat. We observed that mid-proliferative hormone levels enhanced, whereas mid-secretory hormone concentrations reduced, the activity of the LTR. These findings demonstrate that in HIV-1-infected cells, estradiol and progesterone regulate HIV-1 replication most likely by directly altering HIV-1 transcriptional activation. An additional indirect mechanism of sex hormone regulation of cytokine and chemokine secretion cannot be excluded. |
| Databáze: | OpenAIRE |
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