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Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, Proceedings of the National Academy of Sciences of the United States of America 118 (2021). doi:10.1073/pnas.2021366118, info:cnr-pdr/source/autori:Caccuri F.; D'Ursi P.; Uggeri M.; Bugatti A.; Mazzuca P.; Zani A.; Filippini F.; Salmona M.; Ribatti D.; Slevin M.; Orro A.; Lu W.; Lio P.; Gallo R.C.; Caruso A./titolo:Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin/doi:10.1073%2Fpnas.2021366118/rivista:Proceedings of the National Academy of Sciences of the United States of America/anno:2021/pagina_da:/pagina_a:/intervallo_pagine:/volume:118
- Publication Year :
- 2020
-
Abstract
- Significance Immune activation and inflammation are predictors of serious non-AIDS events even in virally suppressed HIV-1−infected individuals. This does not apply to HIV-2−infected patients, who experience a form of attenuated HIV-1 disease. Here, we show that the HIV-1 matrix protein 17 (p17) binds to and activates the common beta chain receptor (βCR). The βCR-activating epitope on p17 is expressed on the matrix protein of HIV-1 ancestors but not on that of HIV-2 and its ancestors. Our finding highlights this epitope as a signature tracing the HIV-1 evolutionary trajectory that may have represented a critical step to enhance the HIV-1 ancestors aggressiveness and early human-to-human transmission. Whether this functional epitope actually marks the pathogenic difference between HIV-1 and HIV-2 needs further investigation.<br />The HIV-1 matrix protein p17 (p17) is a pleiotropic molecule impacting on different cell types. Its interaction with many cellular proteins underlines the importance of the viral protein as a major determinant of human specific adaptation. We previously showed the proangiogenic capability of p17. Here, by integrating functional analysis and receptor binding, we identify a functional epitope that displays molecular mimicry with human erythropoietin (EPO) and promotes angiogenesis through common beta chain receptor (βCR) activation. The functional EPO-like epitope was found to be present in the matrix protein of HIV-1 ancestors SIV originated in chimpanzees (SIVcpz) and gorillas (SIVgor) but not in that of HIV-2 and its ancestor SIVsmm from sooty mangabeys. According to biological data, evolution of the EPO-like epitope showed a clear differentiation between HIV-1/SIVcpz-gor and HIV-2/SIVsmm branches, thus highlighting this epitope on p17 as a divergent signature discriminating HIV-1 and HIV-2 ancestors. P17 is known to enhance HIV-1 replication. Similarly to other βCR ligands, p17 is capable of attracting and activating HIV-1 target cells and promoting a proinflammatory microenvironment. Thus, it is tempting to speculate that acquisition of an epitope on the matrix proteins of HIV-1 ancestors capable of triggering βCR may have represented a critical step to enhance viral aggressiveness and early human-to-human SIVcpz/gor dissemination. The hypothesis that the p17/βCR interaction and βCR abnormal stimulation may also play a role in sustaining chronic activation and inflammation, thus marking the difference between HIV-1 and HIV-2 in term of pathogenicity, needs further investigation.
- Subjects :
- Cell type
Viral protein
Angiogenesis
HIV Antigens
Biology
medicine.disease_cause
gag Gene Products, Human Immunodeficiency Virus
Microbiology
common beta chain receptor
Epitope
Proinflammatory cytokine
Evolution, Molecular
Epitopes
HIV Seropositivity
medicine
Humans
Receptor
Erythropoietin
Cells, Cultured
HIV-1 evolutionary trajectory
Multidisciplinary
Viral matrix protein
Molecular Mimicry
HIV
virus diseases
Biological Sciences
HIV-1 matrix protein p17
Cell biology
human erythropoietin
Molecular mimicry
HIV-1 and HIV-2 ancestors
HIV-2
HIV-1
Common beta chain receptor
Human erythropoietin
Simian Immunodeficiency Virus
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 118
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....cf27c71dfd659103d1b9360fc773f566
- Full Text :
- https://doi.org/10.1073/pnas.2021366118