Trim5α protein restricts both HIV-1 and murine leukemia virus

Yap, Melvyn W.; Nisole, Sébastien; Lynch, Clare; Stoye, Jonathan P.

doi:10.1073/pnas.0402876101

Cited by 414 publications

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“…[4][5][6][7][8][9] As would be expected, TRIM5a from a particular species does not inhibit cognate retroviruses, but it can target retroviruses from other species, thereby contributing to the prevention of inter-species transmission. Human TRIM5a inhibits some retroviruses, such as the equine infectious anemia virus (EIAV) and the so-called 'N strains' of the murine leukemia virus (N-MLV) 4,5,10,11 but it only weakly restricts HIV-1, HIV-2 and many simian immunodeficiency viruses (SIVs), including SIVs from macaques (SIV mac ), from African green monkeys (SIV AGM ) and from chimpanzees (SIV cpz ). 5,12,13 It is likely that the limited restriction range of TRIM5a hu has made it possible for lentiviruses infecting nonhuman primates to cross-species and thrive in humans, thus causing the current HIV pandemic.…”

Section: Introductionmentioning

confidence: 99%

Generation of human TRIM5α mutants with high HIV-1 restriction activity

et al. 2010

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Section: Introductionmentioning

confidence: 99%

Generation of human TRIM5α mutants with high HIV-1 restriction activity

et al. 2010

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“…Additionally, rhTRIM5␣ and agmTRIM5␣ as well as the human variant of TRIM5␣ (huTRIM5␣) were subsequently identified as the factors responsible for restricting the infection by N-tropic MLV in cell lines derived from these species (Hatziioannou et al, 2004;Keckesova et al, 2004;Yap et al, 2004;Song et al, 2005c).…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, the TRIM5␣ proteins from rhesus monkey (rhTRIM5␣) and African green monkey (agmTRIM5␣) have been shown to restrict HIV-1 infection Yap et al, 2004;Song et al, 2005c). Additionally, rhTRIM5␣ and agmTRIM5␣ as well as the human variant of TRIM5␣ (huTRIM5␣) were subsequently identified as the factors responsible for restricting the infection by N-tropic MLV in cell lines derived from these species (Hatziioannou et al, 2004;Keckesova et al, 2004;Yap et al, 2004;Song et al, 2005c).…”

Section: Introductionmentioning

confidence: 99%

“…TRIM5␣-mediated restriction is saturable with high multiplicity of infection (MOI), and the specificity of TRIM5␣-mediated HIV-1 restriction is governed by the recognition of a capsid determinant in the restricted virus similar to the case of Fv1-mediated restriction of MLV infection (Towers et al, 2000;Cowan et al, 2002;Owens et al, 2003Owens et al, , 2004Hatziioannou et al, 2004). However, TRIM5␣-mediated restriction differs from Fv1-mediated restriction in that TRIM5␣-mediated restriction is manifested earlier in the infectious pathway, before the accumulation of reverse transcription products (Shibata et al, 1995;Himathongkham and Luciw, 1996;Cowan et al, 2002;Munk et al, 2002).Specifically, the TRIM5␣ proteins from rhesus monkey (rhTRIM5␣) and African green monkey (agmTRIM5␣) have been shown to restrict HIV-1 infection Yap et al, 2004;Song et al, 2005c). Additionally, rhTRIM5␣ and agmTRIM5␣ as well as the human variant of TRIM5␣ (huTRIM5␣) were subsequently identified as the factors responsible for restricting the infection by N-tropic MLV in cell lines derived from these species (Hatziioannou et al, 2004;Keckesova et al, 2004;Yap et al, 2004;Song et al, 2005c).…”

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TRIM5α Cytoplasmic Bodies Are Highly Dynamic Structures

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Yap

et al. 2007

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Tripartite motif (TRIM)5␣ has recently been identified as a host restriction factor that has the ability to block infection by certain retroviruses in a species-dependent manner. One interesting feature of this protein is that it is localized in distinct cytoplasmic clusters designated as cytoplasmic bodies. The potential role of these cytoplasmic bodies in TRIM5␣ function remains to be defined. By using fluorescent fusion proteins and live cell microscopy, we studied the localization and dynamics of TRIM5␣ cytoplasmic bodies. This analysis reveals that cytoplasmic bodies are highly mobile, exhibiting both short saltatory movements and unidirectional long-distance movements along the microtubule network. The morphology of the cytoplasmic bodies is also dynamic. Finally, photobleaching and photoactivation analysis reveals that the TRIM5␣ protein present in the cytoplasmic bodies is very dynamic, rapidly exchanging between cytoplasmic bodies and a more diffuse cytoplasmic population. Therefore, TRIM5␣ cytoplasmic bodies are dynamic structures more consistent with a role in function or regulation rather than protein aggregates or inclusion bodies that represent dead-end static structures. INTRODUCTIONThe species-specific tropism of many retroviruses is determined by cellular restriction factors present in the cells of the host. One of the most well characterized restriction factors is the murine Fv1 gene, which prevents infection by particular strains of murine leukemia virus (MLV) (Best et al., 1996; for review, see Bieniasz, 2004;Goff, 2004). It is known that restriction by Fv1 involves the recognition of a capsid determinant in MLV (DesGroseillers et al., 1983;Kozak and Chakraborti, 1996). Analysis of Fv1 restriction indicates that restricted MLV strains can generate reverse transcription products but that they are unable to complete subsequent steps in infection (Pryciak and Varmus, 1992) and also that this restriction of infection is saturable, because it can be overcome with high levels of virus (Pincus et al., 1975;Duran-Troise et al., 1977).A similar restriction to human immunodeficiency virus 1 (HIV-1) infection in primates has also been well characterized; and recently, the cellular factor present in the cells of Old World monkeys responsible for restricting infection by HIV-1 was cloned and identified as the cytoplasmic body component tripartite motif (TRIM)5␣ . Restriction of HIV-1 infection by TRIM5␣ resembles restriction of MLV infection by Fv1 in many ways. TRIM5␣-mediated restriction is saturable with high multiplicity of infection (MOI), and the specificity of TRIM5␣-mediated HIV-1 restriction is governed by the recognition of a capsid determinant in the restricted virus similar to the case of Fv1-mediated restriction of MLV infection (Towers et al., 2000;Cowan et al., 2002;Owens et al., 2003Owens et al., , 2004Hatziioannou et al., 2004). However, TRIM5␣-mediated restriction differs from Fv1-mediated restriction in that TRIM5␣-mediated restriction is manifested earlier in the infectious pathway, b...

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“…Interestingly, TRIM5 has been implicated in HIV-1 restriction in primates, and this antiviral effect is mediated through the SPRY domain. 30,31 Antiviral effects have also been reported for other TRIM members, suggesting that the SPRY domain has evolved for anti-viral immunity. Interestingly, the mutations found in FMF patients are also mainly localized in the SPRY domain of Pyrin.…”

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The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1β processing

et al. 2007

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The autoinflammatory disorders Muckle-Wells syndrome, familial cold urtecaria and chronic infantile neurological cutaneous and articular syndrome are associated with mutations in the NALP3 (Cryopyrin) gene, which is the central platform of the proinflammatory caspase-1 activating complex, named the inflammasome. In patients with another autoinflammatory disorder, familial Mediterranean fever (FMF), mutations in the SPRY domain of the Pyrin protein are frequently found. Recent evidence suggests that Pyrin associates with ASC, an inflammasome component, via its Pyrin domain, thereby halting the inflammatory response. This interaction, however, does not explain the effects of mutations of the SPRY domain found in FMF patients. Here we show that the Pyrin SPRY domain not only interacts with NALP3, but also with caspase-1 and its substrate pro-interleukin(IL)-1b. Whereas a Pyrin knockdown results in increased caspase-1 activation and IL-1b secretion, overexpression of the SPRY domain alone blocks these processes. Thus Pyrin binds to several inflammasome components thereby modulating their activity.

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Trim5α protein restricts both HIV-1 and murine leukemia virus

Cited by 414 publications

References 34 publications

Generation of human TRIM5α mutants with high HIV-1 restriction activity

Generation of human TRIM5α mutants with high HIV-1 restriction activity

TRIM5α Cytoplasmic Bodies Are Highly Dynamic Structures

The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1β processing

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