A conserved mechanism of retrovirus restriction in mammals

Towers, Greg J.; Bock, Michael; Martin, Samia; Takeuchi, Yasuhiro; Stoye, Jonathan P.; Danos, Olivier

doi:10.1073/pnas.200286297

Cited by 224 publications

(323 citation statements)

References 31 publications

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“…However, SIV mac encounters postentry restrictions in most New World monkey cells (31). Similar restrictions for some murine leukemia viruses have been observed with human cells (44). By examining the infection of heterokaryons and by performing infections in the presence of competitor viruses, the cellular factors responsible for retroviral restriction have been demonstrated to be dominant and saturable (2,3,15,28,37).…”

supporting

confidence: 53%

Binding and Susceptibility to Postentry Restriction Factors in Monkey Cells Are Specified by Distinct Regions of the Human Immunodeficiency Virus Type 1 Capsid

Owens

Song

Perron

et al. 2004

J Virol

114

118

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In cells of Old World and some New World monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after virus entry. The simian immunodeficiency virus SIV mac is less susceptible to these restrictions, a property that is determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on the surface of the HIV-1 capsid, changing them to the corresponding residues found on the SIV mac capsid. We identified two distinct pathways of escape from early, postentry restriction in monkey cells. One set of mutants that were altered near the base of the cyclophilin A-binding loop of the N-terminal capsid domain or in the interdomain linker exhibited a decreased ability to bind the restricting factor(s). Consistent with the location of this putative factor-binding site, cyclophilin A and the restricting factor(s) cooperated to achieve the postentry block. A second set of mutants that were altered in the ridge formed by helices 3 and 6 of the N-terminal capsid domain efficiently bound the restricting factor(s) but were resistant to the consequences of factor binding. These results imply that binding of the simian restricting factor(s) is not sufficient to mediate the postentry block to HIV-1 and that SIV mac capsids escape the block by decreases in both factor binding and susceptibility to the effects of the factor(s).

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supporting

confidence: 53%

Binding and Susceptibility to Postentry Restriction Factors in Monkey Cells Are Specified by Distinct Regions of the Human Immunodeficiency Virus Type 1 Capsid

Owens

Song

Perron

et al. 2004

J Virol

114

118

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“…50,51 In our hands, N-MLV replication was decreased by overexpression of wild-type TRIM5a hu (Supplementary Figure 1). This effect was greater at relatively high amounts of viral input (for example, 100 ml of virus) than at lower doses such as 25 ml.…”

Section: Restriction Of Other Retrovirusesmentioning

confidence: 58%

“…This effect was greater at relatively high amounts of viral input (for example, 100 ml of virus) than at lower doses such as 25 ml. This is likely due to the well-known effect of saturation of the restriction at high virus doses: 50,52 endogenous TRIM5a hu is saturated by large amount of incoming N-MLV capsids but overexpression of TRIM5a hu restores restriction. That both N-MLV and EIAV were significantly inhibited by overexpressed TRIM5a hu suggests that the endogenous protein is expressed at levels too low for optimal restriction, at least in the absence of interferons.…”

Section: Restriction Of Other Retrovirusesmentioning

confidence: 99%

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

et al. 2010

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“…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, before the accumulation of reverse transcription products (Shibata et al, 1995;Himathongkham and Luciw, 1996;Cowan et al, 2002;Munk et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

TRIM5α Cytoplasmic Bodies Are Highly Dynamic Structures

Campbell

Dodding

Yap

et al. 2007

MBoC

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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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A conserved mechanism of retrovirus restriction in mammals

Abstract: We speculate that these activities have been selected for by retroviral epidemics in the distant past.

Cited by 224 publications

References 31 publications

Binding and Susceptibility to Postentry Restriction Factors in Monkey Cells Are Specified by Distinct Regions of the Human Immunodeficiency Virus Type 1 Capsid

Binding and Susceptibility to Postentry Restriction Factors in Monkey Cells Are Specified by Distinct Regions of the Human Immunodeficiency Virus Type 1 Capsid

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

TRIM5α Cytoplasmic Bodies Are Highly Dynamic Structures

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