Animal hosts deploy diverse mechanisms to sense, evade, and defend against a variety of viral threats. These powerful and highly specialized antiviral strategies have been shaped through millions of years of constant struggle with past viruses. Given that the vast majority of these viruses are now extinct, it is difficult to assess the impact that specific viral infections had on the evolution of our antiviral defenses. Fueled by major advances in sequencing during the last decades, the emerging field of paleovirology have allowed us to take a glimpse into the past and characterize some of these ancient viruses. In particular, through the analysis of endogenous retroviruses (ERVs), we were able to reconstruct two fully functional ancient retroviruses that were in circulation several million years ago (MYA), and uncovered the defense mechanisms that led to their extinction (Blanco-Melo, et al. 2017, 2018). Additionally, by analyzing ancient DNA (aDNA) extracted from archaeological remains, we identified two pathogenic human viruses (HBV and B19V) that were brought into Mexico during the transatlantic slave trade more than 400 years ago (Guzman-Solis, et al. 2021).

The Blanco-Melo lab seeks to decipher the properties of ancient viral infections and model their impact on the evolution of our host antiviral defenses, in order to learn from the past and develop strategies to drive modern viruses similarly extinct.

Current projects in the lab are:

1. Co-option of endogenous viral elements (EVEs): Remnants of past viral infections can be found scattered across animal genomes in the form of EVEs. These viral-like elements are the result of accidental germline invasions, where the integrated viral genome became capable of vertical transmission, survived natural selection and reached fixation. While most EVEs accumulated several inactivating mutations and became subject to genetic drift, a few viral sequences actually provided an advantage to the host and became fixed in the population (Frank & Feschotte. 2017). Most EVEs in animal genomes correspond to endogenous retroviruses (ERVs). Previously, we found that a particular primate ERV (hsaHTenv) was co-opted as an antiviral defense against an ancient retrovirus (HERV-T) through receptor interference (Blanco-Melo, et al. 2017). While this antiviral strategy contributed to the extinction of HERV-T ~11 MYA, it is intriguing that the co-opted ERV is still being expressed and has maintained a functional ORF despite the absence of its initial selective pressure (i.e. HERV-T). We are currently investigating a novel anti-tumor function for hsaHTenv derived from its original one as a regulator of the monocarboxylate transporter MCT1. Additionally, we are characterizing the imunogenic effects of human ERVs and their potencial roles in human disease, particularly in cancer.

2. Viral outbreaks of Colonial Mexico: After the European colonization of the Americas there was a dramatic population collapse of the Indigenous inhabitants caused in part by the introduction of new pathogens. Remarkably, the pathogen(s) responsible for the deadliest epidemics reported in New Spain (the Spanish viceroyalty that corresponds to Mexico, Central America, and the current US southwest states) remain unknown. Through the use of ancient DNA (aDNA) techniques on archeological remains, we previously reconstructed three ancient human parvovirus (B19V) and one hepatitis B virus genomes and found that these viruses were introduced into the Americas as a consequence of the intense transatlantic slave trade that occurred after the European colonization (Guzmán-Solís et al., 2021). In collaboration with the Ávila-Arcos lab at LIIGH, we are continuing our viral discovery efforts in order to identify historically important ancient viruses and understand the impact of these introduced pathogens in the immunologically naïve native population.

Blanco-Melo, D., Gifford, R.J., and Bieniasz, P.D. (2017). Co-option of an endogenous retrovirus envelope for host defense in hominid ancestors. Elife 6. DOI: 10.7554/eLife.22519

Blanco-Melo, D., Gifford, R.J., and Bieniasz, P.D. (2018). Reconstruction of a replication-competent ancestral murine endogenous retrovirus-L. Retrovirology 15, 34. DOI: 10.1186/s12977-018-0416-3

Guzman-Solis, A.A., Villa-Islas, V., Bravo-Lopez, M.J., Sandoval-Velasco, M., Wesp, J.K., Gomez-Valdes, J.A., Moreno-Cabrera, M.L., Meraz, A., Solis-Pichardo, G., Schaaf, P., tenOever, B. R., Blanco-Melo, D., Avila Arcos, M. C. (2021). Ancient viral genomes reveal introduction of human pathogenic viruses into Mexico during the transatlantic slave trade. Elife 10. DOI: 10.7554/eLife.68612

Frank, J.A., Feschotte, C. (2017). Co-option of endogenous viral sequences for host cell function. Curr Opin Virol. 25:81-89. DOI: 10.1016/j.coviro.2017.07.021