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Equine infectious anemia virus Mat protein serves as a Tat cofactor to facilitate viral transcription.
Abstract: Equine infectious anemia virus (EIAV) is a member of the genus of the family and serves as an important model for studying lentiviral pathogenesis. A novel EIAV-encoded protein, designated Mat, was previously identified in our laboratory, yet its biological functions remained unclear. Here, we demonstrate that disruption of Mat moderately reduced EIAV replication in equine monocyte-derived macrophages, and this defect was restored when Mat was supplied in . Further analyses revealed that Mat exhibits nuclear localization and enhances Tat-mediated transcriptional activation of the long terminal repeat (LTR), an essential and conserved step in lentiviral replication, by interacting with viral Tat and the host factor Cyclin T1 (CycT1), but not with the trans-acting responsive RNA element (TAR) within the LTR. Moreover, we found that Mat stabilizes EIAV Tat (eTat) and promotes the association of eTat with both TAR and equine CycT1. These findings indicate that Mat serves as a cofactor of Tat to regulate EIAV replication.IMPORTANCEIn lentiviruses, Tat-mediated activation of the LTR promoter is essential for viral replication. Mechanistically, Tat binds to TAR (a structured RNA at the 5' end of nascent viral transcripts, corresponding to the R region of the LTR), recruits host factors, including CycT1, and facilitates RNA polymerase II elongation, thereby promoting efficient production of full-length viral transcripts required for lentiviral replication. We recently identified an uncharacterized EIAV protein, Mat. Here, we show that Mat inactivation moderately attenuates EIAV replication , and this defect is rescued by ectopic Mat expression. Mat enhances Tat-mediated activation of EIAV LTR activity, and we further confirm that Mat interacts with EIAV Tat (eTat) and equine CycT1 (eqCycT1), stabilizes eTat, and promotes the association of eTat with both TAR and eqCycT1. These results suggest that Mat acts as an eTat cofactor in EIAV transcriptional regulation, providing insights into the complex transcriptional regulatory mechanisms of lentiviruses.
Publication Date: 2026-07-27 PubMed ID: 42505242PubMed Central: PMC13483383DOI: 10.1128/jvi.00828-26Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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Overview
- This study investigates the function of a novel protein called Mat in the equine infectious anemia virus (EIAV), showing that Mat acts as a cofactor for the viral protein Tat to enhance viral gene transcription and replication.
Background
- Equine infectious anemia virus (EIAV) is a lentivirus, belonging to the Retroviridae family, which causes disease in horses and serves as a model for studying lentiviral pathogenesis.
- Lentiviruses rely heavily on the Tat protein to activate transcription from the virus’s long terminal repeat (LTR) promoter, which is critical for viral replication.
- Tat binds to a structured RNA element called TAR in the viral RNA and recruits host factors like Cyclin T1 to facilitate transcription elongation by RNA polymerase II.
- Despite this well-known mechanism, other viral proteins and cofactors involved in regulating EIAV transcription were not fully understood before this study.
Identification and Role of Mat Protein
- The researchers previously discovered an uncharacterized EIAV-encoded protein named Mat in their laboratory.
- They found that inactivating or disrupting Mat moderately reduced EIAV replication in equine monocyte-derived macrophages, a primary cell type infected by EIAV.
- This replication defect was restored when Mat was reintroduced, indicating its functional importance in virus replication.
Mat Protein Mechanism of Action
- Subcellular localization studies showed that Mat is predominantly located in the nucleus, consistent with an involvement in viral gene transcription regulation.
- Mat enhances the transcriptional activation capability of EIAV Tat on the viral LTR promoter, a critical step for effective viral replication.
- Mat physically interacts with the viral Tat protein and the host cell factor Cyclin T1 (CycT1), which is necessary for Tat’s function.
- Unlike Tat, Mat does not bind directly to the TAR RNA element of the LTR, suggesting it modulates transcription through protein-protein interactions rather than RNA binding.
- Mat stabilizes the Tat protein (referred to as eTat in EIAV), preventing its degradation and thus enhancing its activity.
- Mat promotes the formation of a complex between Tat, TAR, and equine Cyclin T1 (eqCycT1), facilitating efficient viral transcript elongation by RNA polymerase II.
Significance and Implications
- This study identifies Mat as a novel cofactor of Tat that contributes to efficient transcriptional regulation in EIAV.
- By stabilizing Tat and promoting its interaction with necessary host factors, Mat enhances viral gene expression and replication.
- Understanding the role of Mat provides new insights into the complex regulatory network governing lentiviral transcription.
- These findings may inform future research on lentiviral biology and potentially contribute to developing antiviral strategies targeting transcriptional regulation in related viruses such as HIV.
Cite This Article
APA
Zhang X, Ma W, Ma X, Guo X, Zhang W, Wang X-F, Wang X.
(2026).
Equine infectious anemia virus Mat protein serves as a Tat cofactor to facilitate viral transcription.
J Virol, 100(8), e0082826.
https://doi.org/10.1128/jvi.00828-26 Publication
Researcher Affiliations
- State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
- State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
- Institute of Western Agriculture, Chinese Academy of Agricultural Sciences, Changji, China.
- China-Kazakhstan Joint Laboratory for Herbivorous Animal Disease Research, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
MeSH Terms
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / physiology
- Infectious Anemia Virus, Equine / metabolism
- Animals
- Horses
- Gene Products, tat / metabolism
- Gene Products, tat / genetics
- Virus Replication
- Viral Transcription
- Gene Expression Regulation, Viral
- Viral Proteins / metabolism
- Viral Proteins / genetics
- Macrophages / virology
- Cyclin T / metabolism
- Cyclin T / genetics
- Terminal Repeat Sequences
- Transcriptional Activation
- RNA, Viral / genetics
Grant Funding
- 32170169 / National Natural Science Foundation of China
- 32172831 / National Natural Science Foundation of China
Conflict of Interest Statement
The authors declare no conflict of interest.
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