Encyclopedia of AIDS

Living Edition
| Editors: Thomas J. Hope, Douglas Richman, Mario Stevenson

Interactions Between HIV-2 and Host Restriction Factors

  • Shmona SimpsonEmail author
  • Sabelle Jallow
Living reference work entry

Later version available View entry history

DOI: https://doi.org/10.1007/978-1-4614-9610-6_41-1


Proteosomal Degradation APOBEC Protein Host Restriction Factor Nascent Virion PRYSPRY Domain 
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Human Immunodeficiency Virus Type 2 (HIV-2) arose during the zoonotic transfer of sooty mangabey Simian Immunodeficiency Virus (SIVsm) on at least eight occasions. Of the resulting eight lineages, HIV-2 A-H, only A and B are endemic, resulting in an estimated one to two million cases, mainly across West Africa. Like HIV-1, HIV-2 is a blood-borne virus, primarily transmitted via heterosexual contact. However, the rate of transmission is substantially lower than that of HIV-1. The majority of HIV-2-infected persons exhibit a phenotype similar to that of HIV-1 long-term nonprogressors. This phenotype is characterized by low to undetectable viral load, with little to no symptoms of immunodeficiency. Nevertheless, 20 % of people living with HIV-2 progress to AIDS in a manner identical to that of HIV-1-infected persons.

Box 1: Defining Host Restriction Factors

Restriction factors are host proteins that mount a first line response to viral infection. HIV specifically antagonises the action of human restriction factors, yet is severely hampered by analogous restriction factors in non-human primates, indicating the pivotal role of restriction factors in cross-species transmission. Restriction factors in the context of HIV-2 infection are characterised by:
  • Derivation from functionally autonomous genes that are unusually variable

  • Sensitivity to immune activation and viral infection resulting in notable changes in their expression

  • The identification of specific viral proteins which directly resist their action

  • A significant decrease in retroviral activity during their overexpression, or attenuation of antagonist-deficient retroviral infection

Experimental infection of macaques has been the dominant animal model for HIV research, resulting in the discovery of several gene expression signatures that interfere with virus transmission and disease progression. The discovery that HIV-1 could not replicate in rhesus macaques despite its similarity to SIV led to the identification of endogenous factors that restrict a number of retroviruses. These proteins, termed host restriction factors (Box 1), are encoded by functionally autonomous genes and tend to be unusually variable. In fact, their counterparts in nonhuman primates are also unusually variable, suggesting that they have evolved under diversifying selection. They are believed to have a role in immunity and inflammation because transcription of the genes encoding these proteins is in most cases stimulated by the innate immune system. The distinctive feature of host restriction factors is that several retroviruses have evolved to resist their action by, in most cases, encoding accessory genes that antagonize their function.

HIV-2 bears more similarity to nonhuman primate lentiviruses than to HIV-1. However, HIV-2 has a highly similar protein structure to HIV-1, and yet is a less pathogenic virus. A better understanding of the interaction between HIV-2 and the human host could play an important role in determining methods to counteract the highly pathogenic HIV-1. Furthermore, the ability of host restriction factors to counteract HIV-2 infection should yield important insights into mechanisms that may reduce virulence of the human immunodeficiency viruses.

Like all primate lentiviruses, HIV-2 possesses the major structural genes gag, pol, and env, which encode the essential proteins for infection and replication. The genome also contains the regulators of viral expression tat and rev, along with four accessory genes, vif, vpx, vpr, nef (Fig. 1) The HIV-2 proteins gag, vif, env, and vpx serve to modify the actions of four major host restriction factors: TRIM5α, APOBEC, Tetherin, and SAMHD1 respectively. The HIV-2 proteins utilize no specific enzymatic function in their roles as antagonists, but rather act as “linker molecules,” connecting host restriction factors to the proteins of cellular pathways that facilitate their sequestration or degradation, and in so doing facilitating viral replication and transmission.
Fig. 1

HIV-2 Genes which antagonise the function of Host Restriction Factors. Structural proteins gag and env, and accessory proteins vif and vpx, are involved in HIV-2 antagonism of host restriction factors

Gag Versus TRIM5α

The HIV Capsid encoded by Gag was previously thought to be an inert packaging shell that protects the genomic material. However, it has emerged that it has several domains that allow interaction with host proteins, such as Cyclophillin A and the cleavage and polyadenylation specific factor 6 (CPSF6). Recent studies into host restriction factors have shown that the Capsid serves as a pathogen-associated molecular pattern (PAMP) for TRIM5α which is a pattern recognition receptor (PRR) (Pertel et al. 2011).

The species-specific retroviral restriction properties of TRIM5α were discovered because HIV-1 could not grow in certain Old World monkey cells. TRIM5α is a member of the Tripartite Motif family of proteins that have the three protein domains: RING, B-Box, and Coiled Coil. TRIM5α has an additional domain, the PRYSPRY/B30.2 domain, that interacts with the retroviral capsid and is responsible for species specificity (Stremlau et al. 2005). Depending on the mammalian species or cell line, TRIM5α may mediate a postentry block of lentiviral replication either before or after reverse transcription. Although the exact mechanism of retroviral restriction is not known, several mechanisms have been proposed with supporting experimental data. Oligomeric TRIMsα recognition of and binding to the incoming intact capsid destabilizes the capsid core, leading to accelerated or premature uncoating, which perturbs reverse transcription. The E3 ligase activity of the RING domain can add ubiquitin molecules to itself and to other proteins, leading to proteasome-mediated protein degradation of the capsid-TRIM complex. TRIM5α is also a pattern recognition receptor that recognizes and binds to the viral capsid, causing a cascade of innate immune signaling that leads to an antiviral state, restricting retroviral replication.

Human TRIM5α has very limited effect on HIV-1 but can restrict N-tropic murine leukemia virus (N-MLV) potently and can limit HIV-2 replication to certain extent. HIV-1 restriction by human TRIM5α maps to the v1 region of the PRYSPRY domain, where a change from arginine or any positively charged residue at position 332 to a proline or any uncharged residue results in potent restriction of both HIV-1 and SIVmac (Yap et al. 2005; Li et al. 2006). Restriction of N-MLV is different from that of HIV-1, in that a larger area of the PRYSPRY domain is involved as well as the coiled coil for restriction of N-MLV mutant L117H (Yap et al. 2005). Human TRIM5α restriction of HIV-2 was also mapped to a single amino acid at position 119 of HIV-2 ROD capsid. HIV-2 viruses with a proline at this position were much more sensitive to human TRIM5α restriction than those without (glutamine or alanine) (Song et al. 2007). Further studies showed that presence of hydrophobic amino acids or those with ring structures were associated with sensitivity to TRIM restriction and those with small side chains or amide groups were linked to TRIM5α resistance (Miyamoto et al. 2011). Three-dimensional modeling of the HIV-1 and HIV-2 capsids showed that the N terminal domains each consist of 7 α-helices from which 3 loops protrude. Position 119 of the HIV-2 capsid is located in the loop between helices 6 and 7. When a proline is present at position 119, the loop between helices 6 and 7 (L6/7) is closer to the loop between helices 4 and 5 (L4/5), a region that directly interacts with cyp A in HIV-1 (Miyamoto et al. 2011). The presence of hydrophobic or ring-structure residues at position 119 of the capsid maintained a certain conformation at L4/5 that is characteristic of sensitive viruses. Curiously, the equivalent position in the N-tropic Murine Leukemia Virus (N-MLV), at position 110, determined viral susceptibility to Human TRIM5α; it was suggested that while HIV-1 and HIV-2 are restricted by different mechanisms, human TRIM5α utilizes a similar mechanism of recognition for N-MLV and HIV-2 (Miyamoto et al. 2011). Further information on TRIM5α in the context of HIV-2 infection is available elsewhere in this chapter (“TRIM5 Alpha and HIV-2 Infection”).

Vif Versus APOBEC

Viral infectivity factor (Vif) is an accessory protein conserved across all primate lentiviruses. Vif-deficient HIV-1 is unable to spread physiologically in relevant macrophage and T-cell cultured cells (Ribeiro et al. 2005). Instead, Vif-deficient virions are produced in normal quantities, but the ability of these virions to infect the subsequent target cell is compromised. This is due to the presence of APOBEC proteins. The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) proteins have several members, A-H, that have been studied in the context of HIV infection. The APOBEC protein most explored in HIV-1 research, APOBEC3G (A3G), is expressed in the majority of cell types. In the absence of Vif, A3G is packaged into nascent virions and acts during reverse transcription to hypermutate viral DNA and decrease cellular cDNA levels. The expression of A3G is sensitive to viral infection and interferon, and so the amount of A3G incorporated into nascent virions is proportionate to its expression level in the producer cell. The net effect of its increased expression, and packaging into nascent virions, is a restriction of HIV-1 infection.

APOBEC proteins mediate their effect utilizing two zinc-coordinating deaminase domains (Z domains) at each end of the protein:
  • The carboxy-terminal Z domain is responsible for deamination.

  • The amino-terminal Z domain mediates A3G’s incorporation into viral particles and is also recognized by HIV-1 Vif.

In order to package itself into assembling virions, A3G uses its amino terminal to bind RNA and attach the Z domain to the NC region of Gag. Following its incorporation into assembling virions, it is transported from the producer cell to the target cell. Once the virion has fused with the target cell, A3G dimerizes and associates with the viral reverse transcriptase complex. A3G then deaminates cytidine residues to uridine in nascent, single-stranded, negative strand cDNA. These uridine-rich transcripts can be degraded. However, if salvaged, during the synthesis of the DNA plus strand, adenosines are incorporated instead of the original guanines resulting in G to A mutations. Up to 10 % of cytidines may be edited resulting in G to A hypermutation of the plus strand sequence, and the loss of genetic integrity. However, not all of the hypermutation occurring in Vif-deficient HIV-1 restriction can be attributed to A3G. A3G has a substantial preference for mutating the second C of CC but not TC. APOBEC3F (A3F), a sister cytidine deaminase to A3G with high sequence identity, favors TC and also serves to induce G to A hypermutations resulting in no functional HIV provirus. The combined effect of A3G and A3F restriction results in hypermutated proviruses that are largely nonfunctional, and to decreased levels of cDNA during Vif-deficient HIV infection. In the case of wild-type HIV-1, the expression of APOBEC proteins has no effect on viral infectivity. Vif is able to bind A3G and A3F, and recruit them to a cellular ubiquitin ligase complex that comprises cullin5, elongins, Rbx2, and an E2 conjugating enzyme. The polyubiqutination of APOBEC proteins results in their proteosomal degradation, and thus thwarts their incorporation into nascent viral particles.

Conversely, A3G and A3F do not play a major role in the replication of Vif-deficient HIV-2. The Vif-deficient HIV-2 virus is able to replicate in the majority of cell lines, including the lymphocyte and macrophage cell lines that are not permissive to Vif-deficient HIV-1. In fact, the Vif of SIVsm (the parent strain of HIV-2) is able to rescue the replication of Vif-deficient HIV-1 in human H9 cells. Though Vif is conserved across all primate lentiviruses, HIV-2 Vif has only 30 % amino acid identity with HIV-1 Vif, and it is evident that APOBEC proteins interact with the two very differently. Regardless of the amount of A3G expressed in a cell, the infectivity of Vif-deficient HIV-2 remains very high (Abada et al. 2005). A substantial reduction in infectivity is only observed in the presence of HIV-2 Vif mutants. These Vif mutants confer a reduction in Vif expression and occur in small motifs essential for Vif function and stability. It is possible that such mutants make Vif more susceptible to APOBEC proteins; however, the infectivity of these mutants is unaltered by increases in A3G expression. Furthermore, regardless of whether a reduction in infectivity is observed in HIV-2 Vif mutant studies, no alteration is observed in the steady state of deaminase. This indicates that the deamination conferred by A3G is ineffective against HIV-2.

Paradoxically, even though A3G is ineffectual for Vif-deficient HIV-2 infectivity, HIV-2 Vif strongly degrades A3G. Furthermore, the effect of HIV-2 Vif is not limited to A3G. HIV-2 Vif can also antagonize A3F, A3H haplotype II, and A3B, with intermediate to high sensitivity, and A3D with low sensitivity. Despite the variation in sensitivity of HIV-2 Vif induced degradation of APOBEC proteins, all known APOBEC proteins except A3A bind to HIV-2 Vif. Now, HIV-2 Vif is better at restricting both A3G and A3F than HIV-1 Vif. In fact, experiments show that HIV-1 Vif reduces A3G by 90 % and HIV-2 Vif reduces A3G by almost 100 %. The effect of HIV-2 Vif antagonism on A3F is even more disparate, showing a 100 % reduction compared with only 83 % by HIV-1 Vif. This is because HIV-2 Vif interacts with separate and distinct domains on APOBEC proteins from those that HIV-1 Vif interacts with. For example, HIV-1 Vif targets a short motif in A3G at position 128–130. This region is essential for HIV-1 Vif’s antagonism of A3G. However, HIV-2 Vif targets multiple, non-neighboring residues found between positions 163 and 321 of A3G (Smith et al. 2014). This indicates that HIV-2 Vif has a broader range of interaction sites, which may result in a greater propensity to degrade A3G than HIV-1 Vif.

It is evident that APOBEC proteins are less able to resist HIV-2 Vif than HIV-1 Vif, and that HIV-2 Vif is better at antagonizing APOBEC proteins than HIV-1 Vif (Wiegand et al. 2004). But despite the complex interplay between HIV-2 Vif and APOBEC proteins, to date there is no physiologically relevant evidence for their interaction in the context of HIV-2 infection of the human host. It is possible that the deamination resulting from APOBEC proteins is countered by another virus mechanism or accessory protein which is presently unknown. Finally the mechanism by which APOBEC proteins are incorporated into nascent HIV-2 virions has yet to be confirmed, and it is very possible that this mechanism may yield important insights into how the effect of APOBEC proteins is managed by HIV-2.

Env Versus Tetherin

The Env protein which forms the HIV-2 envelope comprises transmembrane protein gp36 and glycoprotein gp125 and serves to bind and initiate a conformational change in the host cell membrane facilitating virus to cell fusion. HIV-2 env is not only able to utilize a greater range of coreceptors, but its interaction with these coreceptors leading to virus/cell fusion occurs twice as fast, when compared to that of HIV-1 Env. In addition to its role in virus entry, HIV-2 Env is responsible for a four to sixfold increase in virus export, a function analogous to that of HIV-1 vpu (Abada et al. 2005). Infection of CD4+ T-cells with HIV-1 mutants lacking the accessory gene vpu leads to poor HIV-1 production, and the accumulation of mature virons on cell surfaces and within vacuolar structures. It was observed that protein tetherin was responsible for this retention of vpu-defective HIV-1 virions. The envelope glycoprotein of some HIV-2 isolates is able to stimulate the release of vpu-defective HIV-1 virions from tetherin positive cells.

Tetherin is a type II transmembrane protein which is constitutively expressed on several cell types and is upregulated in response to proinflammatory cytokines. Tetherin is found at the cell membrane from which wild-type HIV-2 is exported in infected cells, and also in intracellular compartments such as the trans-Golgi network and endosomes which package proteins into membrane-bound vesicles. Tetherin is able to facilitate transport between the cell membrane and the Golgi apparatus and endosomes using clathrin adaptors. Anchored at both the N and C terminals to the plasma membrane, the extracellular coiled coil domain protrudes. Acting as a dimer, tetherin cross-links viral membranes, and viral and cellular membranes to each other. In this manner, it is able to tether nascent virons, preventing their release (Fig. 2). Instead, they remain tethered to the infected cell. The virions are then internalized into endosomal compartments where they are degraded. In addition, it is also highly likely that tetherin serves an additional function in cell signaling. As antigen-presenting cells are targets for HIV-2, the degradation of nascent virions in phagosomes likely leads to the presentation of viral particles to the adaptive immune system. Further, the tetherin promotor contains binding sites for NF-AT and NF-kB (IFN and interleukin response elements). As tetherin is induced by signals that also trigger type I IFN production, the induction of the type I IFN response and tetherin is linked. Recent data show that tetherin may act as an innate sensor of viral infections that activates NF-kB to induce an inflammatory response (Hotter et al. 2013).
Fig. 2

Env-mediated Down Regulation of Cell Surface Tetherin. In Env deficient HIV-2 infection, tetherin moves from the ER, through the Golgi network, to the plasma membrane through the anterograde trafficking pathway where it is recycled between the TGN and the cell surface. Tetherin is available to cross link viral membranes, and viral and cellular membranes to each other, resulting in the tethering of nascent virions to the cell. The virions are internalised and degraded. In wild-type HIV-2 infection, HIV-2 Env attaches to tetherin redirecting it away from the plasma membrane and causing its retention in the trans-golgi network. Nascent HIV-2 virions are able to bud from the infected cell

As observed with TRIM and APOBEC proteins, HIV-2 is able to antagonize host restriction factors by the recruitment of ubiquitin ligases, targeting them for degradation. An alternative method employed by HIV-2 to counteract host defenses is by altering the trafficking pathways used by the host factors to prevent their expression at the cell surface. HIV-2 Env does not reduce total cellular levels of tetherin, as studies have yet to find evidence of tetherin degradation. However, HIV-2 Env acts to downregulate the total level of cellular expression of tetherin in two ways: firstly the downregulation of cell-surface tetherin and secondly through tetherin accumulation in the trans-Golgi network, with the net effect of excluding tetherin from virus assembly and export sites. HIV-2 Env attaches its cytoplasmic tail to tetherin, forming a link between it and the clathrin adaptor complex AP-2 and serves to redirect de novo or recycling tetherin away from the plasma membrane and to perinuclear compartments via clathrin-mediated endocytosis (Le Tortorec et al. 2011). However, while Env promotes the release of virions and facilitates subsequent viral infection, this may come at a cost to the virus. In the case of HIV-1, the antitetherin effect is mediated by an accessory protein: vpu. However, HIV-2 Env is a major structural protein which accompanies tetherin along the clathrin-mediated endocytosis pathway, and into its sequestration. This reduction in cellular Env may decrease the levels of Env available during assembly of virus, and thus the amount of virus which can be exported. This is one theory for the reduced virulence of HIV-2.

Vpx Versus SAMHD1

HIV-2 encodes two accessory proteins that are homologous to HIV-1 Vpr: Vpr and Vpx. Vpx is unique to HIV-2, SIVsm, and SIVmac, and arose from gene duplication of Vpr during the evolution of primate lentiviruses (Planelles and Barker 2010). Vpx is considered a paralogue of HIV-1 Vpr. They are both packaged into budding viral particles and are able to assemble into an E3 ligase complex with cellular proteins (Fujita et al. 2010). These functions suggest that Vpx plays an important role in early infection by targeting certain proteins for proteosomal degradation. Early studies showed that Vpx is dispensable for HIV-2 infection of lymphocyte or monocyte derived immortalized cell lines. However, Vpx-deficient HIV-2 shows impaired replication in monocyte-derived macrophages, PBMCs, and primary T-cells. This indicates that Vpx is essential for HIV-2 replication only in nondividing/slow dividing cell lines. Further, though human cells of myeloid lineage and resting CD4 T-cells possess the necessary receptors to allow HIV-1 capture and entry, they are not readily infected by HIV-1. In this case, HIV-1 infection is rescued by the intracellular delivery of Vpx (Sharova et al. 2008). The reason HIV-1 encounters a blockade in non- and slow-dividing cells was found to be due to a host restriction factor: Sterile alpha motif (SAM) and histidine/aspartic acid (HD) domain protein 1 (SAMHD1).

SAMHD1 is found in all cell types and localizes to the nucleus. It possesses nuclease and deoxyribonucleoside triphosphate phosphohydrolase (dNTPase) activity. As a dNTPase, SAMHD1 forms a tetramer and acts to sequester dNTPs, thus keeping them at very low levels outside of the S phase of the cell cycle (Yan et al. 2013). This reduction in cellular dNTP halts reverse transcription (Fig. 3). SAMHD1 also possesses exonuclease activity against single-stranded DNAs and RNAs, and preferentially cleaves 3′ overhangs in double-stranded substrates. This function further contributes to virus restriction by direct cleavage of viral nucleic acids (Beloglazova et al. 2013). SAMHD1 is regulated by phosphorylation at position T592. In cycling cells, SAMHD1 is phosphorylated, and while its dNTPase activity is unaltered, it is unable to block retroviral restriction (White et al. 2013). Phosphorylation is mediated through SAMHD1’s interaction with the cell cycle regulator cyclin-dependent kinase (CDK1). CDK1 is inactive in resting cells, hence explaining why Vpx is only essential for HIV-2 replication in non- or slow-dividing cells. The C-terminal region of SAMHD1 contains a Vpx binding motif, which is important for the ability of Vpx to degrade SAMHD1. Vpx counteracts SAMHD1 restriction by binding to the restriction factor, and coupling with the Cul4/DDB1/DCAF1 ubiquitin ligase complex. This results in the proteosomal degradation of SAMHD1 (Fig. 3). Vpx requires DCAF1 interaction for efficient macrophage infection by HIV-2. Studies on other DCAF-1 interacting proteins revealed that SAMHD1 forms a complex with cyclin L2 which facilitates SAMHD1 interaction with DCAF1. In fact, knockdown of cyclin L2 resulted in a five-fold, threefold, and fourfold reduction in the replication of HIV-1, HIV-2, and Vpx deficient HIV-2, respectively (Kyei et al. 2015). While in HIV-2 infection, Vpx tags SAMHD1 to DCAF resulting in its proteosomal degradation, it is evident that cyclin L2 assists Vpx in proteosomal degradation of SAMHD1.
Fig. 3

SAMHD1 Blocks Reverse Transcription in the Absence of Vpx. In Vpx-deficient HIV-2 infection, SAMHD1 reduces the amount of dNTP available for reverse transcription halting the production of viral protein. In wild-type HIV-2 infection, Vpx couples SAMHD1 with the Cul4/DDB1/DCAF1 ubiquitin ligase complex facilitated by cyclin L2, resulting in proteosomal degradation of SAMHD1. As a result, dNTP is available for viral reverse transcription leading to production of viral proteins

Vpx also antagonizes APOBEC3A (A3A) and interferon regulatory factor 5 (IRF5), providing insight into why A3A is the only APOBEC protein which does not bind to HIV-2 Vif. Unlike A3G, A3A exerts its effect in myeloid cells, monocytes, dendritic cells, and macrophages. Silencing of A3A in primary macrophages, dendritic cells, and monocytes results in an increased susceptibility to HIV-1 and augmented replication of R5 HIV-1 tropic viruses. Further, treatment of myeloid cells with IFNα results in increased resistance to HIV-1 infection which coincides with a threefold increase in A3A expression. The antiviral effect mediated by A3A results in a decrease in viral DNA accumulation. Like A3G, A3A is believed to act as a cytidine deaminse, destroying viral DNA through extensive deamination of cytosine. In addition, A3A exerts a cytotoxic effect by:
  • Inducing strand breaks in genomic DNA which results in cell-cycle arrest

  • Degrading foreign DNA

  • Blocking restrotransposition of LINE-1, Alu, and TLR

Experimental evidence shows that A3A, but not A3G, co-immunoprecipitates with Vpx proteins derived from HIV-2 and SIVmac. That same study concluded that SIVmac Vpx antagonizes A3A by inducing its degradation in the early stages of infection (Berger et al. 2011). Biochemical analysis of A3A activity reveals its enclosure in autophagosomal membrane compartments and cell nuclei (Pham et al. 2013). In the case of IRF5, Vpx inhibits IRF5-mediated transactivation by a mechanism that is not completely understood. IRF5 is involved in the production of proinflammatory cytokines and Type 1 interferon. Expression of Vpx can reduce mRNA levels and protein production of Toll-like receptor-dependent IL6, IL12, and TNFα, which would interfere with the upregulation of interferon-sensitive host genes (Cheng and Ratner 2014).

The interaction of Vpx with SAMHD1, while fascinating, has yet to result in substantial clinically relevant findings. Vpx contains a highly conserved polyproline motif (positions 103–109) which is critical for its effective translation. Mutation of multiple prolines to alanines in this motif resulted in minimal expression of Vpx. Yet, a study of Vpx sequences from HIV-2 progressors and nonprogressors revealed that only one mutation at position 68 reduced SAMHD1 antagonism in vitro. It is possible that further studies of the interaction between Vpx and SAMHD1 in multiple populations may reveal clinically relevant mutations in host or virus that have a clinical impact on the course of HIV-2 disease progression.


It is widely believed that there are many more host restriction factors to be uncovered, and further roles of HIV-2 proteins to be described. It is plausible that the reduced virulence of HIV-2 when compared to HIV-1 may be due to modulation of viral replication by host restriction factors. Furthermore, several HIV-2 proteins alter the course of mutant HIV-1 infection, and in addition, the mutation of HIV-1 amino acids to achieve greater identity to their HIV-2 counterparts substantially alters retroviral replication in several instances. Proteins such as MOV10 and TRIM22 are presently under investigation for their role in retroviral disease progression. Research into TRIM5α, APOBEC, tetherin, and SAMHD1 in the context of HIV-2 infection presents significant scope for therapeutic exploitation. Gene therapies that modify host restriction factors to better restrict retroviral infection and agents that block interactions between antagonistic viral proteins and host restriction factors are attractive approaches for the development of new antiretroviral therapies.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Nuffield Department of MedicineUniversity of OxfordOxfordUK
  2. 2.Medical Research Council LaboratoriesFajara, BakauGambia