Biology subjects

Khan, S. N.

Publications and source records attributed to Khan, S. N..

3 recordsLinked to original sources

bioRxiv2024

Detection of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in New York City

Highly pathogenic avian influenza viruses of the H5N1 clade 2.3.4.4b arrived in North America in the winter of 2021/2022. These viruses have spread across the Americas causing morbidity and mortality in both wild and domestic birds as well as some mammalian species, including cattle. Many surveillance programs in wildlife as well as commercial poultry operations have detected these viruses. Here we conducted surveillance of avian species in the urban environment in New York City. We detected highly pathogenic H5N1 viruses in six samples from four different bird species and performed full genome sequencing. Sequence analysis showed the presence of multiple different genotypes. Our work highlights that the interface between animals and humans that may give rise to zoonotic infections or even pandemics is not limited to rural environments and commercial poultry operations but extends into the heart of our urban centers. ImportanceWhile surveillance for avian influenza viruses is often focused on migratory routes and their associated stop-over locations, or commercial poultry operations, many bird species - including migratory birds - frequent or live in urban green spaces and wetlands. This brings them into contact with a highly dense population of humans and pets providing an extensive urban animal-human interface in which the general public may have little awareness of circulating infectious diseases. This study focuses on virus surveillance at this interface, combined with culturally responsive science education and community outreach.

microbiology↗

bioRxiv2019

TLR4 mediates Il-6 production in irinotecan induced mucositis

IntroductionIrinotecan is a first line chemotherapeutic agent for colorectal carcinoma and well known for debilitating diarrhoea caused by mucositis. Tlr4, a pattern recognition receptor, has been implicated in irinotecan -induced mucositis due to its activation of downstream inflammatory pathways and interaction with luminal microbes. Tlr4 deletion has been reported to attenuate mucosal injury in preclinical models of mucositis, hypothesised to occur by blockade of Il-6 production. As such, the current study aimed to determine the relationship between Tlr4 and Il-6 in the context of irinotecan induced mucositis.\n\nMaterials and methodsArchived ileum and colon tissues from BALB/c wild type (WT) and Tlr4 -/-billy (Tlr4 KO) female mice were used throughout the study. Mice had received single dose of irinotecan (i.p. 270 mg/kg) or vehicle and sacrificed at 6 and 72 hours. Il-6 mRNA and protein expression was determined by qPCR and immunofluorescence, respectively. Data was analysed by Kruskal-Wallis test (qPCR delta CT values) and one-way analysis of variance (ANOVA) (immunofluorescence % area stained).\n\nResultsIl-6 protein expression was significantly reduced in Tlr4 KO mice as compared to WT mice at 6 h in ileum and colon. mRNA expression was not significantly different between groups.\n\nConclusionThese findings support the hypothesis that Tlr4 deletion protects from irinotecan-induced mucositis by ameliorating Il-6 production. The effect appears to be post-transcriptionally mediated, although further research is required to determine if it is via a direct or indirect mechanism. In the future, Il-6 may be targeted therapeutically to ameliorate symptoms of mucositis.

physiology↗

bioRxiv2018

An inhibitor-interaction intermediate of HIV-1 protease, revealed by Isothermal Titration Calorimetry and NMR spectroscopy

Some of drug-resistant mutants of HIV-1 protease (PR), such as a clinically-relevant drug- resistant PR mutant (Flap+(I54V)) containing L10I, G48V, I54V and V82A mutations, produce significant changes in the balance between entropy and enthalpy of the drug-PR interactions, compared to the wild-type (WT) PR. Here, to gain a comprehensive understanding of the entropy-enthalpy compensation effects, we compared nuclear magnetic resonance (NMR), fluorescence spectroscopy and isothermal titration calorimetry (ITC) data of a WT PR with Flap+(I54V) and related mutants: (1) Flap+(I54V); (2) Flap+(I54A) which evolves from Flap+(I54V) in the continued presence of inhibitor yet does not exhibit entropy-enthalpy compensation; and (3) Flap+(I54), a control mutant that contains only L10I, G48V and V82A mutations. Our data indicate that WT and Flap+(I54A) show enthalpy-driven inhibitor-interaction, while Flap+(I54) and Flap+(I54V) exhibit entropy-driven inhibitor interaction. Interestingly, Flap+(I54A) exhibited significantly slower heat flow in the competitive ITC experiment with a strong binder, darunavir, and a weak binder, acetyl-pepstatin, but did not exhibit such slow heat flow in the direct inhibitor-titration experiments. NMR confirmed replacement of the weak binder by the strong binder in a competitive manner. This difference in the heat flow of the competitive binding experiment compared to the direct experiment can only be explained by assuming an inhibitor-bound intermediate pathway. A similar, but attenuated, tendency for slow heat flow was also detected in the competitive experiment with WT. Overall, our data suggests that an inhibitor-bound intermediate affects the entropy-enthalpy compensation of inhibitor-PR interaction.

biochemistry↗