Nucleus remodeling activity is conserved amongst diverse SIV Vpr isolates
- 1UT Health San Antonio: The University of Texas Health Science Center at San Antonio
Abstract
Human immunodeficiency virus (HIV) encodes four accessory proteins that are essential for virus replication in vivo, primarily through the counteraction of host innate immune defense mechanisms. One of these proteins, Vpr, induces constitutive DNA damage repair (DDR) signaling to drive global epigenetic remodeling and activation of transcription programs that enhance HIV-1 promoter activity during acute infection and virus reactivation from latency. Vpr is conserved amongst diverse simian immunodeficiency virus (SIV) strains; however, the evolutionary breadth of Vpr's nucleus remodeling activity has yet to be thoroughly characterized. Here, we investigate a diverse panel of 16 SIV Vpr isolates and demonstrate that 13 out of 16 are capable of significantly activating DDR signaling compared to control infected cells. Moreover, cells infected with these isolates also exhibit increased abundance of two histone marks associated with transcription and euchromatin formation, as well as increased activation of two transcription factors known to be critical for HIV-1 promoter activity. Furthermore, site-directed mutagenesis of a highly homologous SIV Vpr isolate that failed to engage the DDR response revealed previously uncharacterized amino acid residues required for HIV-1 Vpr DDR engagement. Finally, structural modeling and functional analyses revealed that phylogenetically diverse Vpr isolates from SIV African green monkey strains induce nucleus remodeling through an evolutionarily distinct set of amino acid residues. Together, these findings demonstrate that hijacking of DDR responses to promote remodeling of the nuclear environment is a broadly conserved Vpr function.
Related
- Comparative genomics of seven Tenacibaculum maritimum isolates from farmed Atlantic salmon (Salmo salar), Atlantic halibut (Hippoglossus hippoglossus), and lumpfish (Cyclopterus lumpus) in Canada and Norway reveals conserved features
- Single-nucleus profiling reveals age-associated remodeling opposed by parity in the postmenopausal human ovary
- Transcriptomics uncovers outer membrane remodeling as conserved strategy for Burkholderia cenocepacia survival in protozoan and macrophage phagosomes
- Two evolutionary histories in one nucleus: genome remodeling and allelic regulation underlying heterosis in hybrid oil palm
- Complementary Models of Cardiometabolic Stress Reveal Conserved Molecular Programs Driving Cardiac Remodeling
BibTeX
@misc{williford2026nucleus,
title = {{Nucleus remodeling activity is conserved amongst diverse SIV Vpr isolates}},
author = {Z. Williford and E. Leavitt and N. Saladino and M. Johnson and D. Salamango},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.749000},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.749000v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Nucleus remodeling activity is conserved amongst diverse SIV Vpr isolates
AU - Z. Williford
AU - E. Leavitt
AU - N. Saladino
AU - M. Johnson
AU - D. Salamango
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.749000
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.749000v1
AB - Human immunodeficiency virus (HIV) encodes four accessory proteins that are essential for virus replication in vivo, primarily through the counteraction of host innate immune defense mechanisms. One of these proteins, Vpr, induces constitutive DNA damage repair (DDR) signaling to drive global epigenetic remodeling and activation of transcription programs that enhance HIV-1 promoter activity during acute infection and virus reactivation from latency. Vpr is conserved amongst diverse simian immunodeficiency virus (SIV) strains; however, the evolutionary breadth of Vpr's nucleus remodeling activity has yet to be thoroughly characterized. Here, we investigate a diverse panel of 16 SIV Vpr isolates and demonstrate that 13 out of 16 are capable of significantly activating DDR signaling compared to control infected cells. Moreover, cells infected with these isolates also exhibit increased abundance of two histone marks associated with transcription and euchromatin formation, as well as increased activation of two transcription factors known to be critical for HIV-1 promoter activity. Furthermore, site-directed mutagenesis of a highly homologous SIV Vpr isolate that failed to engage the DDR response revealed previously uncharacterized amino acid residues required for HIV-1 Vpr DDR engagement. Finally, structural modeling and functional analyses revealed that phylogenetically diverse Vpr isolates from SIV African green monkey strains induce nucleus remodeling through an evolutionarily distinct set of amino acid residues. Together, these findings demonstrate that hijacking of DDR responses to promote remodeling of the nuclear environment is a broadly conserved Vpr function.
ER -