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HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle."

N6-methyladenosine (m6A) is the most abundant HIV RNA modification but the interplay between the m6A reader protein YTHDF3 and HIV replication is not well understood. We found that knockout of YTHDF3 in human CD4+ T-cells increases infection supporting the role of YTHDF3 as a restriction factor. Overexpression of the YTHDF3 protein in the producer cells reduces the infectivity of the newly produced viruses. YTHDF3 proteins are incorporated into HIV particles in a nucleocapsid-dependent manner permitting the m6A reader protein to limit infection in the new target cell at the step of reverse transcription. Importantly, HIV protease cleaves the virion-incorporated full-length YTHDF3 protein, a process which is blocked by HIV protease inhibitors used to treat HIV infected patients. Mass-spectrometry confirmed the proteolytic processing of YTHDF3 in the virion. Thus, HIV protease cleaves the virion-encapsidated host m6A effector protein in addition to the viral polyproteins to ensure optimal infectivity of the mature virion.

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This article was published in the following journal.

Name: PLoS pathogens
ISSN: 1553-7374
Pages: e1008305

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Medical and Biotech [MESH] Definitions

An ADAMTS protease that contains 15 THROMBOSPONDIN (TS) motifs. It cleaves the PROTEOGLYCANS AGGRECAN and VERSICAN and also functions in protein transport from the ENDOPLASMIC RETICULUM to the GOLGI APPARATUS.

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Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.

An ADAMTS protease similar to ADAMTS5 PROTEIN. It contains a single C-terminal thrombospondin (TS) motif and cleaves AGGRECAN in CARTILAGE. It may also be involved in the destruction of aggrecan in ARTHRITIS.

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