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Ullah, I.

Publications and source records attributed to Ullah, I..

4 recordsLinked to original sources

Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy

Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We could visualize virus spread sequentially from the nasal cavity to the lungs and thereafter systemically to various organs including the brain, which culminated in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct Fab-mediated neutralization, Fc effector interactions of NAbs with monocytes, neutrophils and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2.

immunology

In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission

Early events in retrovirus transmission are determined by interactions between incoming viruses and frontline cells near entry sites. Despite their importance for retroviral pathogenesis, very little is known about these events. We developed a bioluminescence imaging (BLI)-guided multiscale imaging approach to study these events in vivo. Engineered murine leukemia reporter viruses allowed us to monitor individual stages of the retrovirus life cycle including virus particle flow, virus entry into cells, infection and spread for retroorbital, subcutaneous and oral routes. BLI permitted temporal tracking of orally administered retroviruses along the gastrointestinal tract as they traversed the lumen through Peyers Patch to reach the draining mesenteric sac. Importantly, capture and acquisition of lymph-, blood- and milk-borne retroviruses spanning three routes, was promoted by a common host factor, the I-type lectin CD169, expressed on sentinel macrophages. These results highlight how retroviruses co-opt the immune surveillance function of tissue resident sentinel macrophages for establishing infection.

microbiology

An in vitro assessment of anti-SARS-CoV-2 activity of oral preparations of iodine complexes (RENESSANS)

Since the emergence of CoVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determined In Vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule) of an Iodine-complex (Renessans). A monolayer of vero cells were exposed to SARS-CoV-2 in the presence and absence of different concentrations (equivalent to 50, 05 and 0.5 g/ml of I2) of Renessans. Anti-SARS-CoV-2 activity of each of the formulation was assessed in the form of cell survival, SARS-CoV-2-specific cytopathic effect (CPE) and genome quantization. With varying concentrations of syrup and capsule, a varying rate of inhibition of CPE, cells survival and virus replication was observed. Compared to 0.5 g/ml concentration of Renessans syrup, 5 and 50 g/ml showed comparable results where there was a 100% cell survival, no CPEs and a negligible viral replication ({Delta}CT= 0.11 and 0.13, respectively). This study indicates that Renessans, containing iodine, may have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.

microbiology

Bacteriophages can be used as infection control agents: A proof-of concept study involving anti-Acinetobacter baumannii phage

Hospital acquired infections are responsible for morbidity and mortality worldwide. Acinetobacter spp. infections are particularly notorious for complicating patient management in ICU settings. Extremely high mortality rates are associated with Acinetobacter infections because of their resistance to first- and second-line drugs. There is imminent need to develop infections control systems that are specific and environment friendly. Here, we report a proof-of-concept anti-Acinetobacter spp. bacteriophage-based infection control assay that is very target specific as well as innocuous to environment. extensively drug resistant (XDR) Acinetobacter baumannii strain was inoculated at various solid surfaces. A bacteriophage, enriched in the same strain, was applied on the inoculated surfaces. Phenol (carbolic acid) was used as a positive control. We show that bacteriophages can be used as infection control agents. In our assay, they killed XDR Acinetobacter baumannii present on solid surfaces. Our bacteriophage was extremely effective at reducing the CFU of inoculated strain to almost undetectable levels.

microbiology