Best first tweet ever!!! I'm beyond honored to join the @HHMINEWS #GilliamFellows community. From Brazil to the Midwest - it's been a journey! 🥶 .I'm so excited to learn from this amazing group of people and work together to continue pushing science forward! So proud of us!💚.

RT @RockLabTB: Ever wonder why drug-resistant Mycobacterium tuberculosis is less fit than drug-susceptible Mtb? And how the bacterium can e….

The last paper from my phd is now published in @JMolBiol! Working together with Arad Moghadasi, we developed a live cell assay for quantifying viral and cellular deubiquitinase activity

RT @jdhallphd: What a time we had. First in-person gathering for most of them, and me. I love my job @ HHMI, but miss regular facetime with….

RT @ScienceYael: 2 days, 32 talks heard, 1 digital (!) poster presented, many friends made. So happy to attend my first @HHMINEWS science m….

Huge thanks to the @HarrisLabUTHSA team, @JordanBeckerPhD, Arad, Nadine, @Ashley_Auerbach, and @AdamZCheng for all the help throughout the last couple years, so happy to finish 2022 seeing this all come together 💚.

Our results combine to suggest that the birth of A3B at a critical branchpoint in primate evolution may have been a driving force in selecting for an ancestral herpesvirus with an expanded RNR functionality through counteraction of this antiviral enzyme

Finally, we reconstructed the ancestral primate A3B protein and show that it is active and antagonized by the RNRs from herpesviruses that infect humans and Old World monkeys, but not by the RNRs from viruses that infect New World monkeys

We also show that grafting critical residues from human herpesvirus RNRs into the RNRs of New World monkey herpesviruses, which normally lack the ability to counteract A3B, is sufficient to enable binding to human A3 enzymes

To test this, we cloned the RNRs from related herpesviruses that infect primates with or without A3B and examined their ability to counteract different primate A3s. We found that only the RNRs from herpesviruses that infect A3B-encoding species exhibit this functionality

We therefore hypothesized that the repurposing of an ancestral herpesvirus RNR as an A3 antagonist may have been selected by the birth of A3B. If so, this function would be expected to be absent in herpesviruses that infect New World monkeys that naturally lack the A3B gene

Humans encode seven different A3 enzymes, but A3B is unique as the only constitutively nuclear A3 family member. A3B is also the youngest A3 in primates and was likely generated in the common ancestor of Catarrhini (i.e. hominoids and Old World monkeys)

We also show that the direct inhibition of A3B enzymatic activity by viral RNRs requires additional interactions involving a hydrophobic pocket in A3B that is not present in related human A3 family members

Using a panel of chimeric A3 proteins, we show that the RNRs from EBV and KSHV interact with different A3B surfaces in order to promote its relocalization from the nucleus to large cytoplasmic aggregates, away from viral replication compartments

I was curious about the mechanistic conservation and evolutionary origin of this novel innate immune counteraction strategy. Cryo-EM data and in silico predictions seemed to suggest that different viral RNRs counteract A3B by binding to distinct regions near the active site

A year before I started my PhD, @AdamZCheng + team discovered that some large dsDNA herpesviruses like EBV and KSHV are susceptible to APOBEC3B (A3B) restriction and have evolved an unexpected strategy to protect their genomes by repurposing their ribonucleotide reductases (RNRs).

Restriction factors are innate immune proteins that protect cells against incoming viruses. One prototypic class of restriction factors is the APOBEC3 (A3) family of cytidine deaminases, which have mostly been associated with the repression of infections by retroviruses like HIV.

My 1st first-author manuscript is out in @eLife! This project started back in 2019 with the question “what makes a viral protein evolve a new function?” A thread:.

RT @ShanleyRoach: Langlois Lab and company had a blast at Wisc-e-sota 2022 🤓 . @LangloisLab @TristanTNeal @AFranOfScience @JordanBeckerPhD….

RT @aniellefranco: Hoje eu voto por mim, por minhas filhas e por ela❤️✊🏾