The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern pose a major threat to public health, due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts, in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage, or the emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared with the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-α, IL-1β) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. In addition, robust expression of viral nucleocapsid protein and histopathological changes were detected in the lungs of B.1.351-infected mice. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current pandemic, resulting in millions of deaths worldwide. Increasingly contagious variants of concern (VoC) have fueled recurring global infection waves. A major question is the relative severity of the disease caused by previous and currently circulating variants of SARS-CoV-2. In this study, we evaluated the pathogenesis of SARS-CoV-2 variants in human ACE-2-expressing (K18-hACE2) mice. Eight-week-old K18-hACE2 mice were inoculated intranasally with a representative virus from the original B.1 lineage or from the emerging B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), or B.1.1.529 (omicron) lineages. We also infected a group of mice with the mouse-adapted SARS-CoV-2 (MA10). Our results demonstrate that B.1.1.7, B.1.351 and B.1.617.2 viruses are significantly more lethal than the B.1 strain in K18-hACE2 mice. Infection with the B.1.1.7, B.1.351, and B.1.617.2 variants resulted in significantly higher virus titers in the lungs and brain of mice compared with the B.1 virus. Interestingly, mice infected with the B.1.1.529 variant exhibited less severe clinical signs and a high survival rate. We found that B.1.1.529 replication was significantly lower in the lungs and brain of infected mice in comparison with other VoC. The transcription levels of cytokines and chemokines in the lungs of B.1- and B.1.1.529-infected mice were significantly less when compared with those challenged with other VoC. Together, our data provide insights into the pathogenesis of previous and circulating SARS-CoV-2 VoC in mice.

Transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) have been extensively used to investigate the pathogenesis and tissue tropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Neuroinvasion and the replication of SARS-CoV-2 within the central nervous system (CNS) of K18-hACE2 mice is associated with increased mortality; although, the mechanisms by which this occurs remain unclear. In this study, we generated primary neuronal cultures from K18-hACE2 mice to investigate the effects of a SARS-CoV-2 infection. We also evaluated the immunological response to SARS-CoV-2 infection in the CNS of K18-hACE2 mice and mouse neuronal cultures. Our data show that neuronal cultures obtained from K18-hACE2 mice are permissive to SARS-CoV-2 infection and support productive virus replication. Furthermore, SARS-CoV-2 infection upregulated the expression of genes involved in innate immunity and inflammation, including IFN-α, ISG-15, CXCL10, CCL2, IL-6 and TNF-α, in the neurons and mouse brains. In addition, we found that SARS-CoV-2 infection of neurons and mouse brains activates the ZBP1/pMLKL-regulated necroptosis pathway. Together, our data provide insights into the neuropathogenesis of SARS-CoV-2 infection in K18-hACE2 mice.

Present study was designed to explore the influences of different categories of chemical factors, such as organic solvents, oxidizing agents, anionic detergent and dye on persistence of locally isolated coliphages and shigaphages from clinical sewage samples. Thirty percent ethanol initiated 83.20 and 62.86% reduction in the number of coliphage and shigaphage plaques in our study respectively. Chloroform mediated decrease in our observation was 53.13 and 88.33% for coliphages and shigaphages, respectively. The number of the shigaphage plaques was reduced by 62.5% following biphasic diethyl ether (DEE) treatment. About 72.66% of coliphages were deactivated after exposure to biphasic diethyl ether. Exposure of the isolated coliphages and shigaphages to 1% formalin had completely destroyed the viability of the bacteriophages. Coliphage survival in this investigation was 37.5% and 2.4% following treatment with 0.3 and 3.0% hydrogen peroxide respectively. The decrease in overall coliphage and shigaphage population was 95.83% and 94.14% while treated with 0.5% sodium dodecyl sulfate (SDS). The number increased for the viruses infecting E. coli by 9.52% where the number of shigaphages declined by 14.63% while growing in presence of a divalent cation [Ca(NO3)2]. Coliphage and shigaphage populations were diminished by 61. 76% and 53.48% respectively after treatment with the neutral red (0.0075%) followed by exposure to visible light.Bangladesh J Microbiol, Volume 31, Number 1-2,June-Dec 2014, pp 47-52

Bacteriophages can survive under unfavorable conditions and their abilities of survivality are highly diversified. The influence of different physical and chemical conditions, such as temperature, pH and salts on the survivability of coliphages and shigaphages isolated from local clinical sewage samples have been summarized. Temperature at 45°C for 30 min caused 53.13% decrease in the number of coliphages but rather increased the number of shigaphages in present study. Temperature at 56°C for 30 min caused 91.41 and 100% fall in the number of coli- and shigaphages, respectively. pH 4 mediated 96.88% and pH 11 caused 100% decline in the number of plaques for coliphages. On the other hand, number of plaques of shigaphages was diminished by 100% at pH 4 and 91.67% at pH 11. MgCl2, MgSO4 and Na2SO4 salt solutions increased the number of coliphage plaques by 287.5, 125 and 37.5%. On the contrary, the decrease in the number of shigaphages was 79.31, 10.34 and 44.83%, respectively through the treatment. The various physical and chemical conditions investigated in this research have affected the test bacteriophages diversely. Temperature while applied at higher level (56ºC) affected the growth of both coliphages and shigaphages. Acidic and alkaline pH modified coli- and shigaphages' survivality and growth negatively. The three salts in question augmented the growth of isolated coliphages profoundly. However, the same three salts failed to do so for the isolated shigaphages. Dhaka Univ. J. Biol. Sci. 25(2): 185-194, 2016 (July)