Epidemiological studies suggest a correlation between severity of acquired immunodeficiency syndrome (AIDS) and selenium deficiency, indicating a protective role for this anti-oxidant during HIV infection. Here we demonstrate that thioredoxin reductase-1 (TR1), a selenium-containing pyridine nucleotide-disulfide oxidoreductase that reduces protein disulfides to free thiols, negatively regulates the activity of the HIV-1 encoded transcriptional activator, Tat, in human macrophages. We used a small interfering RNA approach as well as a high affinity substrate of TR1, ebselen, to demonstrate that Tat-dependent transcription and HIV-1 replication were significantly increased in human macrophages when TR1 activity was reduced. The increase in HIV-1 replication in TR1 small interfering RNA-treated cells was independent of the redox-sensitive transcription factor, NF-B. These studies indicate that TR-1 acts as a negative regulator of Tat-dependent transcription. Furthermore, in vitro biochemical assays with recombinant Tat protein confirmed that TR1 targets two disulfide bonds within the Cys-rich motif required for efficient HIV-1 transactivation. Increasing TR1 expression along with other selenoproteins by supplementing with selenium suggests a potential inexpensive adjuvant therapy for HIV/AIDS patients.
Surfactant protein A (SP-A) binds to and modulates phagocytosis of Mycobacterium tuberculosis by macrophages. We investigated the relationship between polymorphisms in the collagen regions of SP-A1 and SP-A2 genes and pulmonary tuberculosis. In the present study, seven single nucleotide polymorphisms (SNPs) (4 exonic and 3 intronic) have been identified in the collagen regions of SP-A1 and SP-A2 genes in Indian population. Two intronic polymorphisms, SP-A1C1416T ((p = 0.0000, odds ratio (OR) = 20.767,95% CI: 8.315-OR<51.870) and SP-A2C1382G (p = 0.0054; OR = 3.675, 95% CI: 1.400< OR<9.644), showed significant association with pulmonary tuberculosis (number of patients = 10, number of controls = 7). A redundant SNPA1660G of SP-A2gene showed significant association with pulmonary tuberculosis (number of patients = 17, number of controls = 19, p = 0.0000, OR = 8.94,95% CI: 3.311
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