Biology subjects

Stevens, C. S.

Publications and source records attributed to Stevens, C. S..

3 recordsLinked to original sources

bioRxiv2021

Nipah virus Bangladesh infection elicits organ-specific innate and inflammatory responses in the marmoset model

The common marmoset (Callithrix jacchus) is increasingly recognized as an ideal non-human primate (NHP) at high-biocontainment due to its smaller size and relative ease of handling. Here, we evaluated the susceptibility and pathogenesis of Nipah virus Bangladesh strain (NiVB) infection in marmosets at biosafety level 4. Infection via the intranasal and intratracheal route resulted in fatal disease in all four infected marmosets. Three developed pulmonary edema and hemorrhage as well as multi-focal hemorrhagic lymphadenopathy, while one recapitulated neurologic clinical symptoms and cardiomyopathy on gross pathology. Organ-specific innate and inflammatory responses were characterized by RNA-seq in six different tissues from infected and control marmosets. Notably, a unique transcriptome was revealed in the brainstem of the marmoset exhibiting neurological symptoms. Our results provide a more comprehensive understanding of NiV pathogenesis in an accessible and novel NHP model, closely reflecting clinical disease as observed in NiV patients.

microbiology↗

bioRxiv2021

Zoonotic potential of a novel bat morbillivirus

Morbilliviruses are amongst the most contagious viral pathogens that infect mammals. Metagenomic surveys have identified numerous morbillivirus sequences in bats, but no full-length authentic morbillivirus has been isolated or characterized from bats. Here we detail the discovery of full-length Myotis Bat Morbillivirus (MBaMV) from a bat surveillance program in Brazil. After determining that MBaMV utilizes bat CD150 but not human CD150 as an entry receptor, we generated an infectious clone of MBaMV using reverse genetics. MBaMV exhibited features consistent with other morbilliviruses, including pleomorphic virions, P-editing and the rule-of-six. MBaMV replicated well in human epithelial cell lines in a nectin-4 dependent manner. Surprisingly, MBaMV was able to infect human macrophages in a CD150-independent manner. However, MBaMV was restricted by cross-neutralizing human sera and did not evade the human innate immune system, indicating that while zoonotic spillover into humans may be possible, MBaMV replication in humans would likely be restricted.

microbiology↗

bioRxiv2020

In plain sight: the role of alpha-1-antitrypsin in COVID-19 pathogenesis and therapeutics.

RationaleSARS-CoV-2 entry into host cells is facilitated by endogenous and exogenous proteases that proteolytically activate the spike glycoprotein and antiproteases inhibiting this process. Understanding the key actors in viral entry is crucial for advancing knowledge of virus tropism, pathogenesis, and potential therapeutic targets. ObjectivesWe aimed to investigate the role of naive serum and alpha-1-antitrypsin (AAT) in inhibiting protease-mediated SARS-CoV-2 entry and explore the implications of AAT deficiency on susceptibility to different SARS-CoV-2 variants. FindingsOur study demonstrates that naive serum exhibits significant inhibition of SARS-CoV-2 entry, with AAT identified as the major serum protease inhibitor potently restricting entry. Using pseudoparticles, replication-competent pseudoviruses, and authentic SARS-CoV-2, we show that AAT inhibition occurs at low concentrations compared with those in serum and bronchoalveolar tissues, suggesting physiological relevance. Furthermore, sera from subjects with an AAT-deficient genotype show reduced ability to inhibit entry of both Wuhan-Hu-1 (WT) and B.1.617.2 (Delta) but exhibit no difference in inhibiting B.1.1.529 (Omicron) entry. ConclusionsAAT may have a variant-dependent therapeutic potential against SARS-CoV-2. Our findings highlight the importance of further investigating the complex interplay between proteases, antiproteases, and spike glycoprotein activation in SARS-CoV-2 and other respiratory viruses to identify potential therapeutic targets and improve understanding of disease pathogenesis.

microbiology↗