Abstract
The impact of steroid hormones estrogen and progesterone on human immunodeficiency virus type 1 (HIV-1) replication is well documented. However, the exact mechanism involved in the regulation of HIV-1 replication by estrogen and progesterone is still unclear. In the present study, we wanted to elucidate the molecular mechanisms underlying the modulation of HIV-1 replication by estrogen and progesterone. To achieve this goal, we used real-time quantitative PCR arrays (PCR arrays) to identify differentially expressed host genes in response to hormone treatments that are involved in antiviral responses. Our in vitro results suggest that treatment with high doses of estrogen and progesterone promotes the expression of host antiviral factors Secretory leukocyte protease inhibitor (SLPI) and Serpin family C member 1 (SERPIN C1) among others produced in response to HIV-1 infection. SLPI is an enzyme that inhibits human leukocyte elastase, human cathepsin G, human trypsin, neutrophil elastase, and mast cell chymase. SERPIN C1 is a plasma protease inhibitor that regulates the blood coagulation cascade by the inhibition of thrombin and other activated serine proteases of the coagulation system. A dose dependent downmodulation of HIV-1 replication was observed in monocyte-derived macrophages (MDMs) pre-treated with the two proteins SLPI and SERPIN C1. Further investigations suggests that the host antiviral factors, SLPI and SERPIN C1 act at the pre-integration stage, inhibiting HIV-1 viral entry and leading to the observed downmodulation of HIV-1 replication. Our studies would help identify molecular mechanisms and pathways involved in HIV-1 pathogenesis.
Highlights
The nature of the human immunodeficiency virus (HIV-1) pandemic has changed since its discovery in the 1980s
Our results suggests that treatment with estrogen and progesterone leads to the up-regulation of host antiviral factors, Secretory leukocyte protease inhibitor (SLPI) and SERPIN C1, which act at the pre-integration stage inhibiting human immunodeficiency virus type 1 (HIV-1) viral entry and the observed downmodulation of HIV-1 replication
We used PCR arrays to identify differentially expressed host factors in response to hormone treatment and HIV-1 infection that are involved in innate immune responses such as CX3CL1, SERPIN C1, SLPI, in apoptosis signaling, in natural killer cell signaling activation pathways, interferon stimulated genes (ISG) including inflammatory cytokines, major chemokines, transcription factors and other host factors
Summary
Santanu Biswas 1 , Emily Chen 1 , Yamei Gao 2 , Sherwin Lee 1 , Indira Hewlett 1, * and Krishnakumar Devadas 1, *. Modulation of HIV Replication in Monocyte-Derived Macrophages (MDM) by Host Antiviral Factors.
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