RESUMO
SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.
RESUMO
The present study is focused on the modulation of Mycobacterium bovis BCG-induced inflammatory response by poly-dispersed acid-functionalized single-walled carbon nanotubes (AF-SWCNTs) in macrophages. Flow cytometric and confocal microscopy studies indicated that both BCG and AF-SWCNTs were efficiently internalized by RAW 264.7 and MH-S macrophage cell lines and were essentially localized in the cytoplasmic area. BCG-induced production of reactive oxygen species (ROS) and nitric oxide by the two cell lines was significantly inhibited by AF-SWCNTs. Using RT-PCR technique, a marked decline was observed in the expression of BCG-induced pro-inflammatory genes COX-2, iNOS, TNF-α, IL-6, and IL-1ß upon treatment with AF-SWCNTs. Results of gelatin zymography indicated that the AF-SWCNTs treatment also induced a marked decline in BCG-induced release of matrix metalloproteinases MMP-2 and MMP-9 by the two macrophage cell lines. The anti-inflammatory effect of AF-SWCNTs in downregulating BCG-induced inflammatory response was further validated in murine peritoneal macrophages. Treatment with AF-SWCNTs led to a steep decline in BCG-induced NO production in murine peritoneal macrophages in vitro as well as in vivo. Peritoneal macrophages isolated from mice treated with BCG and AF-SWCNTs had a significantly lower intracellular expression of COX-2 as compared to the peritoneal macrophages derived from mice treated with BCG alone. Taken together, our results demonstrate a potent anti-inflammatory effect of AF-SWCNTs in alleviating BCG-induced inflammatory responses in macrophages in vitro and in vivo.
