Dataset Information

Cellular IP₆ Levels Limit HIV Production while Viruses that Cannot Efficiently Package IP₆ Are Attenuated for Infection and Replication.

ABSTRACT: HIV-1 hijacks host proteins to promote infection. Here we show that HIV is also dependent upon the host metabolite inositol hexakisphosphate (IP₆) for viral production and primary cell replication. HIV-1 recruits IP₆ into virions using two lysine rings in its immature hexamers. Mutation of either ring inhibits IP₆ packaging and reduces viral production. Loss of IP₆ also results in virions with highly unstable capsids, leading to a profound loss of reverse transcription and cell infection. Replacement of one ring with a hydrophobic isoleucine core restores viral production, but IP₆ incorporation and infection remain impaired, consistent with an independent role for IP₆ in stable capsid assembly. Genetic knockout of biosynthetic kinases IPMK and IPPK reveals that cellular IP₆ availability limits the production of diverse lentiviruses, but in the absence of IP₆, HIV-1 packages IP₅ without loss of infectivity. Together, these data suggest that IP₆ is a critical cofactor for HIV-1 replication.

SUBMITTER: Mallery DL

PROVIDER: S-EPMC6931105 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Cellular IP6 Levels Limit HIV Production while Viruses that Cannot Efficiently Package IP6 Are Attenuated for Infection and Replication.

Mallery Donna L DL Faysal K M Rifat KMR Kleinpeter Alex A Wilson Miranda S C MSC Vaysburd Marina M Fletcher Adam J AJ Novikova Mariia M Böcking Till T Freed Eric O EO Saiardi Adolfo A James Leo C LC

Cell reports 20191201 12

HIV-1 hijacks host proteins to promote infection. Here we show that HIV is also dependent upon the host metabolite inositol hexakisphosphate (IP6) for viral production and primary cell replication. HIV-1 recruits IP6 into virions using two lysine rings in its immature hexamers. Mutation of either ring inhibits IP6 packaging and reduces viral production. Loss of IP6 also results in virions with highly unstable capsids, leading to a profound loss of reve ...[more]

PMID: 31851928

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Cellular IP₆ Levels Limit HIV Production while Viruses that Cannot Efficiently Package IP₆ Are Attenuated for Infection and Replication.

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Cellular IP<sub>6</sub> Levels Limit HIV Production while Viruses that Cannot Efficiently Package IP<sub>6</sub> Are Attenuated for Infection and Replication.