Michel Perron's research while affiliated with Harvard Medical School and other places
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Publications (16)
Human TRIM5alpha restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5alpha that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to...
An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5alpha. We modeled the structure of the B-box 2 domain of TRIM5alpha based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most o...
Two of the most well-known genetic mechanisms in mammalian cells which control the susceptibility of cells to productive infection by retroviruses and lentiviruses rely on the cellular Fv1 and Ref1 restriction factors, which act, after viral entry, to prevent productive infection through their interactions with viral capsid (CA) sequences. While pr...
The host cell factors TRIM5alpha(hu) and Fv-1 restrict N-tropic murine leukemia virus (N-MLV) infection at an early postentry step before or after reverse transcription, respectively. Interestingly, the identity of residue 110 of the MLV capsid determines susceptibility to both TRIM5alpha(hu) and Fv-1. In this study, we investigate the fate of the...
TRIM5alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5alpha on HIV-1 infection. In African Americans, the frequencies of two non-coding SNP variant alleles in exon...
Cyclophilin A (Cyp A) binds the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein and contributes to the early events in virus replication in some cells. The retroviral restriction factor TRIM5alpha can inhibit the early, post-entry phase of infection by associating with the incoming viral capsid. Cyp A has been proposed to prevent re...
Tripartite motif 5α (TRIM5α) restricts some retroviruses, including human immunodeficiency virus type 1 (HIV-1), from infecting
the cells of particular species. TRIM5α is a member of the TRIM family of proteins, which contain RING, B-box, coiled-coil
(CC), and, in some cases, B30.2(SPRY) domains. Here we investigated the abilities of domains from T...
Human TRIM5α (TRIM5αhu) potently restricts N-tropic (N-MLV), but not B-tropic, murine leukemia virus in a manner dependent upon residue 110 of the
viral capsid. Rhesus monkey TRIM5α (TRIM5αrh) inhibits N-MLV only weakly. The study of human-monkey TRIM5α chimerae revealed that both the v1 and v3 variable regions
of the B30.2/SPRY domain contain pote...
Primate tripartite motif 5α (TRIM5α) proteins mediate innate intracellular resistance to retroviruses. In humans, TRIM5 is located in a paralogous cluster that includes TRIM6, TRIM34, and TRIM22. Although TRIM6 and TRIM34 orthologs are found in other mammals, TRIM5 has to date been identified only in primates. Cow cells exhibit early blocks to infe...
The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus infection; susceptibility to these
blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5α variants from Old World monkeys specifically
associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5α B30.2 do...
The TRIM5α proteins of humans and some Old World monkeys have been shown to block infection of particular retroviruses following
virus entry into the host cell. Infection of most New World monkey cells by the simian immunodeficiency virus of macaques
(SIVmac) is restricted at a similar point. Here we examine the antiretroviral activity of TRIM5α or...
Retroviruses encounter dominant postentry restrictions in cells of particular species. Human immunodeficiency virus type 1
(HIV-1) is blocked in the cells of Old World monkeys by TRIM5α, a tripartite motif (TRIM) protein composed of RING, B-box
2, coiled-coil, and B30.2(SPRY) domains. Rhesus monkey TRIM5α (TRIM5αrh) more potently blocks HIV-1 infec...
Reovirus replication and assembly are thought to occur within cytoplasmic inclusion bodies, which we call viral factories. A strain-dependent difference in the morphology of these structures reflects more effective microtubule association by the mu2 core proteins of some viral strains, which form filamentous factories, than by those of others, whic...
Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including humans. This block is mediated by a dominant host factor that targets the viral capsid soon aft...
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 r...
Host cell barriers to the early phase of immunodeficiency virus replication explain the current distribution of these viruses among human and non-human primate species. Human immunodeficiency virus type 1 (HIV-1), the cause of acquired immunodeficiency syndrome (AIDS) in humans, efficiently enters the cells of Old World monkeys but encounters a blo...
Citations
... The IN enzyme itself is only part of a larger complex of proteins, called the pre-integration complex, that includes viral dsDNA, IN, Vpr, and matrix proteins; host proteins BANF1 and LEDGF/p75 are also associated [106,107]. The host factor TRIM5α is known to interfere with uncoating prior to integration in some non-human primates, however, the human TRIM5α gene is not able to do so [108]. Human genes that are required for integration represent an interesting mechanism for the future of HIV replication inhibition. ...
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... Some TRIM proteins regulate the activity of key signaling proteins involved in various steps of the autophagy pathway [37]. TRIM5α not only directly recognizes the HIV capsid protein to mediate its autophagic degradation but also promotes the degradation of the HIV capsid protein by regulating autophagy-related molecules [38]. TRIM16 promotes antiviral autophagy by promoting the activation of the P62-NRF2 axis [39]. ...
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... Replacement of the HIV-1 H4/5L with the corresponding sequence from SIVmac, an RM-derived SIV strain insensitive to restriction by RM TRIM5α, restored HIV-1 infectivity in monkey cells [240,241]. Single amino acid changes in the H4/5L also enhance HIV-1 infection in cells expressing RM TRIM5α [240,242,243]. One such change, H87Q, is present in circulating HIV-1 strains [161]. ...
... Tripartite motif 5 alpha (TRIM5α) is a species-specific restriction factor that is known to act against human immunodeficiency virus type 1 (HIV-1) infection in Rhesus monkeys and N-tropic murine leukemia virus (N-MLV) infection in humans [1,2]. TRIM5α comprises four major domains: RING, B-box, coiled-coil, and B30.2 (PRY/SPRY) [3][4][5]. ...
... It will be interesting to examine which of the polymorphism at position 208, already known to be associated with multiple phenotypes [30,51,52], or the 342 position, for which there is to our knowledge no associated phenotype, is actually associated with differences in interferon induction. It should be noted that the substitution of proline for a serine at the 208 position was shown to result in a protein exhibiting a thermosensitive phenotype for some of its function [53]; it may simply be the case in its role for the control of the interferon induction. ...
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... Tripartite motif 5 alpha (TRIM5α) is a species-specific restriction factor that is known to act against human immunodeficiency virus type 1 (HIV-1) infection in Rhesus monkeys and N-tropic murine leukemia virus (N-MLV) infection in humans [1,2]. TRIM5α comprises four major domains: RING, B-box, coiled-coil, and B30.2 (PRY/SPRY) [3][4][5]. The RING domain provides ubiquitin E3 ligase activity, and mutations in this region affect the ubiquitination of target proteins [6,7], thereby impacting the ability of TRIM5α to restrict viral DNA synthesis [8,9]. ...
... African green monkey Vero cells are typically used as target cells for SARS-CoV-2 [3,[70][71][72], but they are resistant to HIV-1 vector infection due to the TRIM5α host restriction factor [73][74][75]. Therefore, the susceptibilities of human 293T, HeLa, and TE671 cells to the pseudotyped HIV-1 vector were analyzed. These cell lines are frequently used as target cells for pseudotyped vectors [8,41,76,77]. ...
... The accessory proteins in HIV-1 are Vif, Vpr, Vpu, Nef (and Vpx in HIV-2) [21][22][23]. Many HIV restriction factors have been discovered, well-known example include (APOBEC3) family of protein especially APOBEC3G, tripartite-motif-containing 5α (TRIM5α), and tetherin/bone marrow stromal cell antigen 2 (BST2) [24][25][26][27]. The new ones include Zinc-finger antiviral protein (ZAP), Serine incorporator 3 and 5 (SERINC3/5) and RPRD2 (also called RNA-associated early-stage antiviral factor, REAF) [28][29][30]. ...
... However, the study found that Caspase-6 can promote three major types of programmed cell death in IAV infection by binding to RIPK3 and strengthening the formation of the PANoptosis complex. TRIM34 is a member of the tripartite motif (TRIM) family [113]. Many TRIM family members exhibit E3 ubiquitin ligase activity [114]. ...
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... TRIM5a binds to the capsid via the unstructured v1 loop within its B30.2 domain (Biris et al., 2012;Sebastian and Luban, 2005). Experiments swapping the v1 loop between TRIM5a orthologs indicated that it is critical for recognition of capsid from many retroviruses (Ohkura et al., 2006;Perron et al., 2006;Sawyer et al., 2005). In Old World monkeys and hominoids, rapid evolution of TRIM5a is concentrated within this v1 loop (Sawyer et al., 2005; Figure 1A). ...
