Evolutionary Trajectories of Primate Genes Involved in HIV Pathogenesis

Ortiz, Millán; Guex, Nicolas; Patin, Étienne; Martin, Olivier; Xenarios, Ioannis; Ciuffi, Angela; Quintana-Murci, Lluı́s; Telenti, Amalio

doi:10.1093/molbev/msp197

Cited by 50 publications

(66 citation statements)

References 61 publications

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“…This process, called positive selection, occurs during A3G interaction with Vif [70], TRIM5α interaction with CA, and BST-2 interaction with Vpu, Nef and Env [28,71]. Paleovirological studies are believed to contribute to the better understanding of how viral infections over time have guided the evolution of the host immune system [72].…”

Section: Genetic Conflict-dependent Adaptation Of the Immune Systemmentioning

confidence: 99%

How Samhd1 changes our view of viral restriction

Laguette¹,

Benkirane²

2012

Trends in Immunology

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Recent studies have uncovered sterile alpha motif and HD domain 1 (SAMHD1) as the restriction factor that blocks HIV-1 replication in myeloid cells. In contrast to previously identified HIV-1 restriction factors, SAMHD1 does not meet a countermeasure developed by HIV-1. However, HIV-2 and certain simian immunodeficiency virus (SIV) strains express the auxiliary protein Vpx that potently blocks SAMHD1. It is therefore perplexing why this function has been lost or not acquired during the course of lentiviral evolution. This article summarizes the similarities and differences between SAMHD1 and other HIV-1 restriction factors, while highlighting the new questions that are emerging about the crosstalk between restriction factors and innate immune responses. Intrinsic cellular defenses and the viral arsenalHIV was identified as a human pathogen 28 years ago [1]. As a result of the inability of the human host to mount a coordinated immune response to the virus, infection by HIV usually results in chronic activation of the immune system that paradoxically allows for poorly controlled viral replication and immune exhaustion: the hallmark of AIDS. HIV-1 has evolved from SIVcpz, which causes AIDS in its natural chimpanzee host, whereas HIV-2 has evolved from SIVsm, which replicates to high levels in its natural simian host without causing disease [2] (Box 1). Hence, it is possible to speculate that lentiviruses and their host immune systems undergo an evolutionary co-adaptation to establish an equilibrium that will permit efficient spread without killing the host. However, tolerance to the infection is a multifactorial process that requires a fertile ground in the host as much as specific features of the virus. Here, we review the recent advances related to how host restriction factors may influence immune sensing and response against HIV. In particular, we examine the recent identification that the immune modulator SAMHD1 is the HIV restriction factor operating in myeloid cells, which are key players in the immune response during viral infection. A not so fertile ground?Upon entry into the human host, viruses are confronted with numerous blocks that oppose their replication (Figure 1). The first line of defense to be triggered is the so-called 'intrinsic' immune system. The intrinsic immune system includes proteins that detect the presence of the assailant pattern recognition receptors (PRRs), [Box 2] and which initiate a subsequent immune response, as well as proteins referred to as restriction factors that are directly devoted to arresting the replication cycle of the virus. To date, four restriction factors have been identified that specifically block HIV-1 replication: tripartite motif (TRIM)5α, apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts (APOBEC3G) (A3G), bone marrow stromal cell antigen 2 (BST-2) (also known as tetherin) and SAMHD1 [3][4][5][6][7]. Host restriction factor characteristicsTRIM5α interacts with...

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Section: Genetic Conflict-dependent Adaptation Of the Immune Systemmentioning

confidence: 99%

How Samhd1 changes our view of viral restriction

Laguette¹,

Benkirane²

2012

Trends in Immunology

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“…Comparison of the primate TRIM5a gene sequences suggests that residues not only in the SPRY domain but also in the CC domain have been subjected to strong positive selection during evolution. 19,49,50 Studies by the Trono and Stoye groups, using interspecies TRIM5a chimeric derivatives, demonstrate a possible cooperativity between the SPRY and CC domains to determine the specificity of TRIM5a-mediated retroviral restriction. 41,51 How the CC domain affects specificity is unclear.…”

Section: Capsid Recognition By Trim5 Proteinsmentioning

confidence: 99%

Recent Insights into the Mechanism and Consequences of TRIM5α Retroviral Restriction

Sastri

Campbell

2011

AIDS Research and Human Retroviruses

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The cellular factor TRIM5a inhibits infection by numerous retroviruses in a species-specific manner. The TRIM5a protein from rhesus macaques (rhTRIM5a) restricts infection by HIV-1 while human TRIM5a (huTRIM5a) restricts infection by murine leukemia virus (MLV). In owl monkeys a related protein TRIM-Cyp restricts HIV-1 infection. Several models have been proposed for retroviral restriction by TRIM5 proteins (TRIM5a and TRIMCyp). These models collectively suggest that TRIM5 proteins mediate restriction by directly binding to specific determinants in the viral capsid. Through their ability to self-associate TRIM5 proteins compartmentalize the viral capsid core and mediate its abortive disassembly via a poorly understood mechanism that is sensitive to proteasome inhibitors. In this review, we discuss TRIM5-mediated restriction in detail. We also discuss how polymorphisms within human and rhesus macaque populations have been demonstrated to affect disease progression of immunodeficiency viruses in these species.

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“…Coiled-coil domains are found in many cellular proteins and are characterized by heptad repeats denoted (abcdefg) n with, typically, hydrophobic residues at positions a and d and polar/charged amino acids at positions e and g. Such domains are predicted to form ␣-helices with amphipathic properties responsible for homomultimerization (28). Finally, the PRYSPRY region directly binds to retroviral capsids, and species-specific sequence variations or engineered changes in its sequence can modify the spectrum of retroviruses restricted by given TRIM5␣ orthologues (21,25,38,50).Although the prominent role of the PRYSPRY domain in dictating the range of TRIM5␣-mediated restriction is well established, comparative analyses of the sequences of primate TRIM5␣ genes reveal that residues located not only in this but also the coiled-coil domain have been subjected to positive selection during evolution (14,26,33). Correspondingly, a study of interspecies TRIM5␣ chimeric derivatives pointed to a possible influence of the coiled-coil domain on the specificity of murine leukemia virus (MLV) restriction (50).…”

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confidence: 99%

“…Although the prominent role of the PRYSPRY domain in dictating the range of TRIM5␣-mediated restriction is well established, comparative analyses of the sequences of primate TRIM5␣ genes reveal that residues located not only in this but also the coiled-coil domain have been subjected to positive selection during evolution (14,26,33). Correspondingly, a study of interspecies TRIM5␣ chimeric derivatives pointed to a possible influence of the coiled-coil domain on the specificity of murine leukemia virus (MLV) restriction (50).…”

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The Specificity of TRIM5α-Mediated Restriction Is Influenced by Its Coiled-Coil Domain

Maillard

Ecco

Ortiz

et al. 2010

J Virol

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Retroviruses are both powerful evolutionary forces and dangerous threats to genome integrity. As such, they have imposed strong selective pressure on their hosts, notably triggering the emergence of restriction factors, such as TRIM5␣, that act as potent barriers to their cross-species transmission. TRIM5␣ orthologues from different primates have distinct retroviral restriction patterns, largely dictated by the sequence of their C-terminal PRYSPRY domain, which binds the capsid protein of incoming virions. Here, by combining genetic and functional analyses of human and squirrel monkey TRIM5␣, we demonstrate that the coiled-coil domain of this protein, thus far essentially known for mediating oligomerization, also conditions the spectrum of antiretroviral activity. Furthermore, we identify three coiled-coil residues responsible for this effect, one of which has been under positive selection during primate evolution, notably in New World monkeys. These results indicate that the PRYSPRY and coiled-coil domains cooperate to determine the specificity of TRIM5␣-mediated capture of retroviral capsids, shedding new light on this complex event.The genomes of higher organisms, including primates, contain large numbers of endogenous retroviruses, remnants of past infections established in their germ lines over millions of years (13). Exogenous retroviruses are still an ongoing threat, as illustrated by the human immunodeficiency virus (HIV) pandemic. Retroviruses have thus subjected higher species to formidable selective pressures, leading to the emergence of a number of host-encoded antiviral factors (42). TRIM5␣ is one such factor, which can restrict a range of retroviruses in a virusand species-specific fashion (9,16,31,34,36,40,49). Although the mechanism of TRIM5␣ action is still not fully understood, it is known that it binds to and multimerizes around incoming capsids, inducing their premature uncoating (3,5,30,37). The accelerated disassembly of the capsid impairs reverse transcription (RT), and the viral genome is also prevented from migrating to the cell nucleus (1,16,36,39,43).TRIM5␣ encompasses a RING finger, a B-box type II and a coiled-coil domain, which together form the so-called RBCC or tripartite motif (TRIM), upstream of a C-terminal PRYSPRY domain (24,27). Each of these regions has been demonstrated to participate in the antiviral function of TRIM5␣, and yet a full understanding of their respective contributions is still lacking. A RING domain is often found in proteins that function as E3 ubiquitin ligases and was demonstrated to promote TRIM5␣ auto-ubiquitination and to regulate protein turnover (4, 10, 44). Deletion of the RING domain significantly affects restriction activity, although the exact role of the ubiquitin pathway in restriction is not fully understood (1,3,29,32,43). The B-box II domain plays an essential function in TRIM5␣ activity partly by mediating the higher-order self-assembly of TRIM5␣, which potentiates restriction (6,11,19,29). The coiled-coil region promotes the formation of mu...

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Evolutionary Trajectories of Primate Genes Involved in HIV Pathogenesis

Cited by 50 publications

References 61 publications

How Samhd1 changes our view of viral restriction

How Samhd1 changes our view of viral restriction

Recent Insights into the Mechanism and Consequences of TRIM5α Retroviral Restriction

The Specificity of TRIM5α-Mediated Restriction Is Influenced by Its Coiled-Coil Domain

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