High expression of Rex-orf-I and HBZ mRNAs and bronchiectasis in lung of HTLV-1A/C infected macaques
Year: 2025
Type: article
Abstract: HTLV-1 type-A rarely causes lung disease in humans, whereas HTLV-1 type-C is more frequently associated with respiratory failure and premature death. We investigated the genetic basis of HTLV-1C morbidity by constructing a chimeric HTLV-1A/C oI-L encompassing the highly divergent type C orf-I. We demonstrate that systemic infectivity of HTLV-1A and HTLV-1A/C oI-L is equivalent in macaques, but viral expression in lungs is significantly higher in HTLV-1A/C oI-L infection. In addition, bronchoalveolar-lavage immune cell dynamics differs greatly with neutrophils and monocytes producing TNF-α in HTLV-1A/C oI-L , but producing IL-10 in HTLV-1A infection. Animals infected with HTLV-1A/C oI-L develops bronchiectasis at 10 months from infection, but at the same timepoint those infected with HTLV-1A do not. HTLV-1A/C oI-L expressed a 16 kDa fusion protein (p16C) via a doubly spliced, Rex-orf-IC, mRNA able to shield T-cells from efferocytosis, a monocyte function that mitigates inflammation via clearance of apoptotic cells. The Rex-orf-IC mRNA is expressed as more frequent in the lung of HTLV-1A/C oI-L than HTLV-1A infected animals. Since defective efferocytosis is associated with lung obstructive pathologies, the data raise the hypothesis that p16C may contribute to the lung morbidity observed in HTLV-1C infection.
Source: Nature Communications
Authors: Sarkis Sarkis, Anna Gutowska, Mohammad Arif Rahman, Luca Schifanella, Katherine C. Goldfarbmuren, Massimiliano Bissa, Ramona Moles, Christina Ramirez, Elijah F. Edmondson, Andrew Warner, Melvin Doster, Isabela Silva de Castro, Robyn Washington-Parks, Sophia Brown, Joshua Kramer, Matthew W. Breed, Kristin E. Killoran, Yogita Jethmalani, Leonid Serebryannyy, Damian FJ. Purcell, Cynthia A. Pise-Masison, Genoveffa Franchini
Institutions: National Cancer Institute, Center for Cancer Research, Frederick National Laboratory for Cancer Research, University of Mississippi Medical Center, Clemson University, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, The University of Melbourne, Peter Doherty Institute
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4414543155