HIV-1 restriction by SERINC5

Cano-Ortiz, Lucía; Luedde, Tom; Münk, Carsten

doi:10.1007/s00430-022-00732-x

Cited by 5 publications

(3 citation statements)

References 84 publications

(142 reference statements)

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“…However, most cellular molecules identified to interact with reovirus FAST proteins are broadly expressed, including adaptors in the branched actin assembly network mentioned above and Annexin A1, which interacts with reptilian orthoreovirus FAST protein p14 and promotes fusion pore expansion (52)(53)(54). While restriction factors directed towards FAST proteins have not yet been identified, several cellular molecules have been proposed to restrict HIV-1 infection, some of which are expressed in specific cell types (reviewed in (75)(76)(77)(78)). Additional studies, perhaps identifying and comparing .…”

Section: Discussionmentioning

confidence: 99%

Multiple rotavirus species encode fusion-associated small transmembrane (FAST) proteins with cell type-specific activity

Veletanlic¹,

Sartalamacchia²,

Diller³

et al. 2023

Preprint

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Fusion-associated small transmembrane (FAST) proteins are viral nonstructural proteins that mediate cell-cell fusion to form multinucleated syncytia. We previously reported that human species B rotavirus NSP1-1 is a FAST protein that induces syncytia in primate epithelial cells but not rodent fibroblasts. We hypothesized that the NSP1-1 proteins of other rotavirus species could also mediate cell-cell fusion and that fusion activity might be limited to cell types derived from homologous hosts. To test this hypothesis, we predicted the structure and domain organization of NSP1-1 proteins of species B rotavirus from a human, goat, and pig, species G rotavirus from a pigeon and turkey, and species I rotavirus from a dog and cat. We cloned these sequences into plasmids and transiently expressed the NSP1-1 proteins in avian, canine, hamster, human, porcine, and simian cells. Regardless of host origin of the virus, each NSP1-1 protein induced syncytia in primate cells, while few induced syncytia in other cell types. To identify the domains that determined cell-specific fusion activity for human species B rotavirus NSP1-1, we engineered chimeric proteins containing domain exchanges with the p10 FAST protein from Nelson Bay orthoreovirus. Using the chimeric proteins, we found that the N-terminal and transmembrane domains determined the cell type specificity of fusion activity. Although the species and cell type criteria for fusion activity remain unclear, these findings suggest that rotavirus species B, G, and I NSP1-1 are functional FAST proteins whose N termini play a role in specifying the cells in which they mediate syncytia formation.

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Section: Discussionmentioning

confidence: 99%

Multiple rotavirus species encode fusion-associated small transmembrane (FAST) proteins with cell type-specific activity

Veletanlic¹,

Sartalamacchia²,

Diller³

et al. 2023

Preprint

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“…Group M and group N HIV-1s are derived from SIV of chimpanzees (SIVcpz), while group O and group P are the results of spillover of SIV of gorillas (SIVgor) ( 1 , 3 , 4 ). To halt retroviral replication, vertebrates use several cellular restriction factors ( 5 – 9 ). It is ill-defined whether the low prevalence of non-M HIVs is associated with the activity of antiviral factors such as the capsid-binding TRIM5α, which may limit their spread among humans.…”

mentioning

confidence: 99%

The cyclophilin A-binding loop of the capsid regulates the human TRIM5α sensitivity of nonpandemic HIV-1

Twizerimana,

Becker,

Zhu

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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The rather few cases of humans infected by HIV-1 N, O, or P raise the question of their incomplete adaptation to humans. We hypothesized that early postentry restrictions may be relevant for the impaired spread of these HIVs. One of the best-characterized species-specific restriction factors is TRIM5α. HIV-1 M can escape human (hu) TRIM5α restriction by binding cyclophilin A (CYPA, also known as PPIA, peptidylprolyl isomerase A) to the so-called CYPA-binding loop of its capsid protein. How non-M HIV-1s interact with huTRIM5α is ill-defined. By testing full-length reporter viruses (Δ env ) of HIV-1 N, O, P, and SIVgor (simian IV of gorillas), we found that in contrast to HIV-1 M, the nonpandemic HIVs and SIVgor showed restriction by huTRIM5α. Work to identify capsid residues that mediate susceptibility to huTRIM5α revealed that residue 88 in the capsid CYPA-binding loop was important for such differences. There, HIV-1 M uses alanine to resist, while non-M HIV-1s have either valine or methionine, which avail them for huTRIM5α. Capsid residue 88 determines the sensitivity to TRIM5α in an unknown way. Molecular simulations indicated that capsid residue 88 can affect trans -to- cis isomerization patterns on the capsids of the viruses we tested. These differential CYPA usages by pandemic and nonpandemic HIV-1 suggest that the enzymatic activity of CYPA on the viral core might be important for its protective function against huTRIM5α.

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“…Cano-Ortiz and colleagues described in detail newest insight in the evolution and expression of SERINC proteins. Specifically, they focused on SER3 and SER5, which inhibit fusion pore formation during entry of human immunodeficiency virus (HIV) into target cells [ 2 ]. Next to HIV, amphotropic murine leukemia virus (MLV) and influenza A virus have also been shown to be restricted by SER5.…”

mentioning

confidence: 99%