Our star post-doc, Victoria, gave a fantastic talk at ASV this year! BTW, the paper should *finally* be out soon.
Laboratory of Functional Viromics (LETKO)
@fviromics.bsky.social
Dr. Michael Letko’s Laboratory of Functional Viromics | we study zoonotic potential of novel viruses. For more information, check out our website: https://labs.wsu.edu/lofv/
Host overlap was the strongest ecological correlate of reassortment, suggesting that opportunities for divergent viral lineages to meet matter more than prevalence alone. Of course, it's not all ecology! Molecular compatibility between genome segments acted as a second filter. (2/3)
This is an impressive study!
Steph N. Seifert, PhD@stephseifertphd.bsky.social · 3mo agoLargest data synthesis effort for hantavirus and arenavirus surveillance ever put together! Proud to have this paper up; while the dataset and analyses on hantaviruses is especially timely, we started this project when @davidsimons.bsky.social received an FIR through @viralemergence.org in 2023. 🐀🦠
New alphaCoV receptor out today in nature! Very cool! www.nature.com/articles/s41...
Heart-nosed bat alphacoronaviruses use human CEACAM6 to enter cells - Nature
Human CEACAM6, which is widely expressed in the lung, is identified as a receptor used by the spike proteins of Cardioderma cor (heart-nosed bat) alphacoronaviruses to enter cells.
nature.com
Our mini-review for Journal of Virology’s “new voices in virology” collection is out now. We highlight our lab’s mission, approaches, successes and visions for the future. doi.org/10.1128/jvi....
Exploring coronavirus cell entry with functional viromics | Journal of Virology
In November of 2002, patients presenting atypical pneumonia were admitted to hospitals in Guangdong Province in the People's Republic of China (1). By April of 2003, a novel causative agent was isolat...
doi.org
A big thank you to Dr. Nick Catanzaro for visiting the LoFV this week and sharing his cool science!
Big thanks to Vic Jefferson, Nick Catanzaro, Ralph Baric and Michael Letko @fviromics.bsky.social and big congrats to @jarelelgin.bsky.social , our talented PhD student who led the work!! 🥳🥳
The bat viruses with the closest spike or loop2 to that of nvHKU5r-CoV were also sampled in provinces with primary mink fur processing and wholesale hubs, further implicating fur farming as an important risk factor for virus spillover.
Lastly we did comprehensive recombination and molecular dating analysis to explore the origins of this nvHKU5r-CoV. Our findings support that the virus transmitted from bats to mink within the last decade, consistent with an expansion of mink fur farming in China.
AlphaFold3 co-structure predictions were also consistent with entry when this single mutation was introduced, revealing the likely molecular interaction that enables hACE2 compatibility.
Using a safe, replication competent VSV system expressing the nvHKU5r-CoV spike we did passaging in mixed cells expressing both Pabr and hACE2. To our surprise, the spikes acquired a single mutation on the loop2, R548S, which enabled hACE2 usage!
Then we asked, since ACE2 ortholog usage seems to shift quite easily in these viruses, could nvHKU5r-CoV potentially use human ACE2?
We further confirmed our pseudovirus results with luciferase reporter live virus, showing that nvHKU5r-CoV specifically replicated well in both PabrACE2 and nvACE2 expressing cells.
Impressively, AlphaFold3 predictions of RBD-ACE2 pairs were very consistent with pseudovirus results! RBDs with ACE2 entry had consistent binding footprints while RBDs without entry were predicted to bind inaccessible parts of the ACE2s.
...the only two long loop2 RBDs that can use nvACE2 being nvHKU5r-CoV and Q265, but not WZ2! This shows that loop2 is a key determinant for enabling the use of non-bat ACE2s.
Taking these RBDs in the lab, we show with pseudovirus assays that all HKU5r-CoVs can use their native P abramus ACE2, but only few can use mink ACE2, especially ones with long loop2s...
This part of the RBD corresponds to a loop in the RBD structure called loop2, known to have different lengths between HKU5r-CoVs. By examining the evolution of the loop2 we show a single deletion to a shorter genotype which has in turn recombined into many different RBDs.
However, just like all CoVs merbecoviruses are notorious for recombining parts of their genome, especially the spike. Looking more closely, we detected one small part of the RBD where nvHKU5r-CoVs were curiously closer to another bat virus, Q265!
The mink HKU5 virus (nvHKU5r-CoV) was sampled in Shendong and seems to be overall closest to different bat HKU5s sampled in P. abramus bats across south and east China. 🦇 When focusing on the spike and RBD, one virus, WZ2, sampled in Zhejiang, is the single closest relative.
New preprint alert!! 🚨🚨🚨in collaboration with the Letko @fviromics.bsky.social and Baric labs! Just in case you're tired of sarbecoviruses, this time we looked at ACE2-using merbecoviruses! specifically the first HKU5r-CoVs detected in mink a couple of years ago. www.biorxiv.org/content/10.1...
Structural and phenotypic plasticity of the RBD loop2 region is a key determinant for HKU5r-CoVs’ emergence in mink
The emergence of novel coronaviruses from animal reservoirs continues to pose a significant zoonotic threat. Here, we investigate the evolutionary origins and virological properties of a recently repo...
biorxiv.org
New pre-print! Where did the HKU5 viruses recently reported in mink come from and where might they go next? In this collaboration with the Sato lab, we explore the recombinant origins of mink HKU5 viruses and test what it would take for human ACE2 use. Intermediate hosts are important for zoonosis!
Structural and phenotypic plasticity of the RBD loop2 region is a key determinant for HKU5r-CoVs' emergence in mink
The emergence of novel coronaviruses from animal reservoirs continues to pose a significant zoonotic threat. Here, we investigate the evolutionary origins and virological properties of a recently repo...
shorturl.at
Excited to share our study reporting the first Sin Nombre virus (SNV) genome sequences from the Northwestern U.S., and the first ever from a vole host. www.biorxiv.org/content/10.1...
First Sin Nombre virus (Orthohantavirus sinnombreense) genome sequences from the Northwestern United States
We report the first Sin Nombre virus (SNV) genome sequences from the Northwestern United States and the first SNV sequences recovered from voles. Analysis of samples collected from 189 individual rode...
biorxiv.org
If you haven’t already, you should check out our latest study identifying the host receptor used by merbecoviruses that circulate European and Asian hedgehogs. It’s a surprising finding that unlocks the entire group of viruses for researchers to study further!
Aminopeptidase N is a receptor for hedgehog merbecoviruses
Merbecoviruses, closely related to the highly pathogenetic Middle East Respiratory Syndrome Coronavirus (MERS-CoV), circulate in hedgehogs throughout Europe and Asia, raising concerns about zoonotic t...
biorxiv.org
This was a large team effort. Big thank you to our structural collaborator, James Rini at University of Toronto, Craig Wilen at Yale, the Baric lab at UNC, our Italian collaborators for discovering these viruses and sharing cool sequence data, and of course, Vic, the talented postdoc in my lab.(6/6)
