Preprints (x2): Oropouche virus

Oropouche orthobunyavirus (OROV) - a little-known oft-ignored peribunyavirus - has stepped up on stage to make itself known over the past year. https://www.science.org/content/article/why-did-obscure-virus-explode-latin-america-new-study-offers-clues

We have 2 pre-prints up on BioRXIV related to OROV.

The first one was posted last month. Kaleigh, Zach, and Maris have been working with OROV on the neuro angle for a while now. Since our publication of Lrp1 as a receptor for OROV, we’ve been studying its role in neuronal infection. Twitter thread on this paper is here.

Connors, K.A., M.R. Pedlow, Z.D. Frey, J.J. McGaughey, G.K. Amarasinghe, W.P. Duprex, L. D’Aiuto, Z.P. Wills, and A.L. Hartman. Characterization of neural infection by Oropouche orthobunyavirus. Posted 10/12/24. bioRxiv https://www.biorxiv.org/content/10.1101/2024.10.11.617875v1. (Preprint)

Since then, we migrated to BlueSky. Find us at: @roguerifter.bsky.social

Cindy now has a preprint that just went live! This is placental work related to her K01. Great collab with Crissy Megli! More to come, including a bluesky thread!! Can’t stop my excitement!!!!!

Megli, C, R.K. Zack, J. McGaughey, R.M. Hoehl, T. Snisky, A.L. Hartman, and C.M. McMillen. Oropouche virus infects human placenta explants and trophoblast organoids. Posted 11/17/24. bioRxiv. 2024.11.16.623866 https://www.biorxiv.org/content/10.1101/2024.11.16.623866v1.

Thankful!

We have a lot of talented folks in the lab. For “Boss’s Day”, I received the Pittsburgh-famous burnt almond torte AND homemade edible BL/6 and CD1 mice! So thankful to work with this great crew :-)

Kaleigh's second paper is published!

The 2nd Connors et al. paper of 2024 is now out!!

JCI Insight - possibly the most painful journal to work with to date in my career - but it is out in “print” officially!

Kaleigh wrote a great tweet-orial about it here.

This was and is a fun collaboration. The whole goal of developing the models over the years is to use them for testing countermeasures. This is the second study working with Jim Crowe’s group at Vanderbilt to evaluate neutralizing anti-RVFV mAbs in one of our disease models. The first was in the pregnant rat model.

This latest paper is the first to evaluate mAbs in the context of aerosol exposure and neurological disease - a very high bar for protection. This is just the beginning because we have additional studies planned.

Hartman Lab is looking to hire!

Within the next few months:

Lab Manager (bachelor’s or MS degree + experience)

and/or

Science Project Manager (PhD degree)

Until the jobs are officially posted on the Pitt website, find my informal description of the positions here.

Please reach out to me directly if you are interested! We are always looking for fun, dynamic folks to join our group. Sense of humor is a requirement!

2024 Summer Lab outing

Really fun summer outing this to Picklesburgh and the Pirate Game!

**Caroline was the honorary Hartman Lab mascot for the evening

***We even have our very own lab shirts this year***

Sheep vs human placenta

We have a new paper out this week - a study led by Cindy McMillen. The goal of the study was two-fold. First, do sheep and human placenta differ in their overall permissivity to RVFV infection (and could this explain the seeming discrepancy between the frequency of fetal infections in the two species)? Secondly, are live-attenuated strains (some of which are the basis for human/veterinary vaccines) still able to infect placenta from either species (and could this provide an indicator of potential safety)?

Direct comparisons between human and sheep placenta have not really been done before, at least in a systematic fashion. So Cindy set out to collect placenta from local farms and the local women’s hospital.

These twins with their mama are part of this study

Devin with placenta collection cooler

Sheep placenta prior to dissection

Nobody really wants to come into our lab due to this type of stuff

Dissected and plated villi

Here’s the papa

Dyanmic placenta duo

This is actually a cow placenta (not featured in the current manuscript)

twinsies

Sheep villi before dissection

Find the full paper here: Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal-fetal placental interface

I have a twitter thread on this here where I discuss our findings. Check out the whole paper. We also have some fantastic science art done by Hayley Nordstrom.

ASV 2024 Columbus / THE Ohio State University

ASV was in Columbus OH this year. That meant CVR Party Bus. No photos of the CVR Party Bus exist but we may have had CVR-colored solo cups on board.

Our lab was represented by Kaleigh and Cade on night 1 with flash talks & posters (double-duty). On the last day, I pinch-hit for Cindy and then Austin knocked it out of the park after me.

We enjoyed having former lab member Devin Boyles joining us for the week!!!

Fantastic week of networking - I forgot how much fun ASV meetings can be!

CVR Trainee Day

I have been (rightfully) called out by my folks for not updating the website in FOREVER and now so many cool things have happend that I am embarrassed. This is called the PI walk of shame. We have had a ton of great things going on. We’ve also been barreling down towards a facility shutdown, so….that’s my excuse. Here’s my attempt at catchup!

In June, we had CVR Trainee Day. Organized by our trainees to highlight their work. They put the whole thing together - schedule, speakers, food, games (bingo) prizes. It literally brought tears to my eyes with how good of a job they did. Dang, we have some great trainees! They love being in CVR and it is evident.

Kaleigh and Rachael were part of the organizing committee. Rachael, Maris, Cade, and Neal all gave presentations.

The Organizers from 3 CVR labs

Rachael gave the first talk of the day!

Cade talking LACV!

Maris’s first time presenting her work :-)

And Neal, who just finished his freshman year at Pitt, also gave his first talk!

Also Neal was given a special award from Paul Duprex, CVR Director!

Congrats Neal!!!

Hartman Lab group photo

All CVR Photo

More photos in the Gallery

Connors et al. #1

Kaleigh has several fantastic studies that are in the publication process. So we are going to call 2024 the “Year of Connors et al”. She has worked really hard over the past couple of years to develop several novel experimental systems for use in our lab. The first one is the rat brain slice culture system that she validated and adapted for our use to study neurotropic bunyaviruses.

Journal of General Virology: Acute Rift Valley fever virus infection induces inflammatory cytokines and cell death in ex vivo rat brain slice culture

I posted about it on Twitter (X) which you can read about here.

What continues to amaze me about this is the fact that these slices are viable for at least 14 days, and Kaleigh did a lot of validation to understand what is happening in the cultures over time. In fact, we use the slices for infection studies after they have been in culture for 10 days because this give the tissue time to calm down from the trauma of slicing. The brains are from 6 day old rat pups, which is why they are able to stay viable for a long time. Similar slices from adult animals would likely not stay viable.

We plan to use these to test therapeutics in brain slices prior to in vivo testing. We hope this gives us a model that is intermediate between immortalized cell lines and cumbersome in vivo BSL-3 studies.

Kaleigh also produces the most beautiful fluorescent images of anyone in the lab (**Zach can certainly rival her for primary neuron images!). Look at these images from cleared slices. Nuclear filaments with active caspase 3 are always striking.

Using the vibratome to slice the brains is pretty cool. Here are some photos of a brain stabilized in agar and then mounted on a cork (See, the PI’s wine consumption comes in handy!). Also, a photo of Zach learning how to slice the brains.