An intracellular block to primate lentivirus replication

Stoye, Jonathan P.

doi:10.1073/pnas.192449399

Cited by 45 publications

(25 citation statements)

References 26 publications

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“…Human TRIM5␣ is less effective than the macaque homologue at inhibiting HIV-1 (16) but, as previously hypothesized (15), it might be required for Ref1 activity. We used real-time reverse transcription-PCR to determine if decreased TRIM5␣ expression explained decreased Ref1 activity in 17H1 cells, but we found less than a twofold difference compared with the parental cell line (data not shown).…”

Section: Fig 1 Selection Strategy For Isolating Ref1-deficient Te67mentioning

confidence: 90%

Selection for Loss of Ref1 Activity in Human Cells Releases Human Immunodeficiency Virus Type 1 from Cyclophilin A Dependence during Infection

Sayah¹,

Luban

2004

J Virol

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Section: Fig 1 Selection Strategy For Isolating Ref1-deficient Te67mentioning

confidence: 90%

Selection for Loss of Ref1 Activity in Human Cells Releases Human Immunodeficiency Virus Type 1 from Cyclophilin A Dependence during Infection

Sayah¹,

Luban

2004

J Virol

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“…It is tempting to speculate which regions of the CA proteins of other viruses interact with restricting molecules such as Lv1, which has phenotypic similarity to Fv1 (2,9,18,49). The region of CA affecting Fv1 binding runs from the end of helix 4 (amino acid 82) through the start of helix 7 (amino acid 117).…”

Section: Discussionmentioning

confidence: 99%

Retroviral Capsid Determinants of Fv1 NB and NR Tropism

Stevens¹,

Bock²,

Ellis³

et al. 2004

J Virol

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The specificity determinants for susceptibility to resistance by the Fv1 n and b alleles map to amino acid 110 of the murine leukemia virus CA protein. To study the interaction between Fv1 and CA, we examined changes in CA resulting in the loss of susceptibility to Fv1 resistance in naturally occurring NB-and NR-tropic viruses. A variety of amino acid changes affecting Fv1 tropism were identified, at CA positions 82, 92 to 95, 105, 114, and 117, and they all were mapped to the apparent exterior of virion-associated CA. These amino acids may form a binding surface for Fv1.The Fv1 gene is one of a series of mouse genes, originally described in the early 1970s, that control the susceptibility of mice to murine leukemia virus (MLV) infection (32,34 nr , found in a few inbred strains of mice and apparently also in some wild mice, restricts B-tropic MLV and some, but not all, N-tropic viruses (28,48). In this paper, we will refer to N-tropic viruses that are not restricted by Fv1 nr as being NR tropic.Fv1 acts in a cell-autonomous manner to restrict virus replication (44), but the precise mechanism for restriction is unclear. It has been shown that viral replication is blocked at a stage after virus entry into the cell and before the integration of newly synthesized viral DNA into the host genome (22, 41). The block to infection is not absolute in vitro, but the number of infected cells is reduced by a factor of 50 to 1,000 (17). When expressed at natural levels, e.g., in mouse fibroblast lines, neither Fv1 n nor Fv1 b shows significant in vitro restriction of NB-tropic MLV.Genetic studies initially suggested that the target for Fv1 restriction is the MLV capsid (CA) protein (20, 43). Subsequent studies indicated that viral tropism is determined by a pair of adjacent amino acids, at positions 109 and 110, in CA (10, 40). A more recent study has shown that position 110 is the most important residue for N and B tropism (29). N-tropic MLV has an Arg residue at this position, and B-tropic MLV has a Glu residue. The determinants for NB and NR tropism have not been fully characterized.The Fv1 gene was cloned a few years ago (3) and was found to have sequence similarity to a family of endogenous retroviruses called HERV-L (60% identity over 1.3 kb) or MuERV-L (1, 3). Based on its position within the element and the presence of a major homology region (3), Fv1 apparently encodes a Gag-related protein. Gag proteins bind tightly to each other via interaction domains during virus assembly (35), which suggests a possible mechanism for Fv1's action on MLV CA (16). To date, however, there is no direct evidence for the binding of Fv1 to CA. Biochemical analyses are greatly complicated by the extremely low natural expression levels of Fv1 in vivo. We have therefore taken a genetic approach to analyzing the viral determinants of NB and NR tropism, using a rapid fluorescence-activated cell sorting (FACS)-based approach for Fv1 testing (5), in an attempt to delineate the region(s) of CA that interacts with Fv1. MATERIALS AND METHODS Cel...

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“…Other capsid-binding proteins, such as cyclophilin A in the case of HIV-1, can modify the degree of restriction (33,34,49,55). Third, restriction is mediated by dominant host factors, the activity of which can be titrated by the introduction of virus-like particles containing proteolytically processed capsid proteins of the restricted viruses (4,6,9,13,29,33,46,54).…”

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confidence: 99%

The B30.2(SPRY) Domain of the Retroviral Restriction Factor TRIM5α Exhibits Lineage-Specific Length and Sequence Variation in Primates

Song

Gold

Ó'hUigín

et al. 2005

J Virol

184

214

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Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5␣, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5␣ has recently been shown to mediate innate intracellular resistance to retroviruses, an activity dependent on the integrity of the B30.2 domain, in particular primate species. An examination of the sequences of several TRIM proteins related to TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the B30.2 domain. Species-specific variation in TRIM5␣ was analyzed by amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5␣ B30.2 v1 region in Old World primates and in v3 in New World monkeys. We observed substitution patterns indicative of selection bordering these particular B30.2 domain variable elements. These results suggest that occasional, complex changes were incorporated into the TRIM5␣ B30.2 domain at discrete time points during the evolution of primates. Some of these time points correspond to periods during which primates were exposed to retroviral infections, based on the appearance of particular endogenous retroviruses in primate genomes. The results are consistent with a role for TRIM5␣ in innate immunity against retroviruses.

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An intracellular block to primate lentivirus replication

Cited by 45 publications

References 26 publications

Selection for Loss of Ref1 Activity in Human Cells Releases Human Immunodeficiency Virus Type 1 from Cyclophilin A Dependence during Infection

Selection for Loss of Ref1 Activity in Human Cells Releases Human Immunodeficiency Virus Type 1 from Cyclophilin A Dependence during Infection

Retroviral Capsid Determinants of Fv1 NB and NR Tropism

The B30.2(SPRY) Domain of the Retroviral Restriction Factor TRIM5α Exhibits Lineage-Specific Length and Sequence Variation in Primates

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