scholarly journals Evolutionary rate shifts suggest species-specific adaptation events in HIV-1 and SIV

2017 ◽  
Author(s):  
Maoz Gelbart ◽  
Adi Stern
Keyword(s):  
Evolutionary Rate ◽  
Virus Transmission ◽  
Restriction Factors ◽  
Species Barrier ◽  
New Host ◽  
Major Barrier ◽  
Viral Adaptation ◽  
Rate Deceleration ◽  
Species Specific ◽  
Hiv 1

AbstractThe process of molecular adaptation following a cross-species virus transmission event is currently poorly understood. Here, we identified 137 protein sites that experienced deceleration in their rate of evolution along the HIV-1/SIV phylogeny, likely indicating gain-of-function and consequent adaptation. The majority of such events occurred in parallel to cross-species transmission events and varied between HIV-1 groups, indicating independent adaptation strategies. The evolutionary rate decelerations we found were particularly prominent in accessory proteins that counteract host antiviral restriction factors, suggesting that these factors are a major barrier to viral adaptation to a new host. Surprisingly, we observed that the non-pandemic HIV-1 group O, derived from gorillas, exhibited more rate deceleration events than the pandemic group M, derived from chimpanzees. We suggest that the species barrier is higher when the genetic distance of the hosts increases. Our approach paves the way for subsequent studies on cross-species transfers in other major pathogens.

scholarly journals Site-Specific Evolutionary Rate Shifts in HIV-1 and SIV

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1312
Author(s):  
Maoz Gelbart ◽  
Adi Stern
Keyword(s):  
Evolutionary Rate ◽  
Species Barrier ◽  
Epistatic Interactions ◽  
Site Specific ◽  
Genome Wide ◽  
Rate Acceleration ◽  
A Genome ◽  
Rate Deceleration ◽  
A Site ◽  
Hiv 1

Site-specific evolutionary rate shifts are defined as protein sites, where the rate of substitution has changed dramatically across the phylogeny. With respect to a given clade, sites may either undergo a rate acceleration or a rate deceleration, reflecting a site that was conserved and became variable, or vice-versa, respectively. Sites displaying such a dramatic evolutionary change may point to a loss or gain of function at the protein site, reflecting adaptation, or they may indicate epistatic interactions among sites. Here, we analyzed full genomes of HIV and SIV-1 and identified 271 rate-shifting sites along the HIV-1/SIV phylogeny. The majority of rate shifts occurred at long branches, often corresponding to cross-species transmission branches. We noted that in most proteins, the number of rate accelerations and decelerations was equal, and we suggest that this reflects epistatic interactions among sites. However, several accessory proteins were enriched for either accelerations or decelerations, and we suggest that this may be a signature of adaptation to new hosts. Interestingly, the non-pandemic HIV-1 group O clade exhibited a substantially higher number of rate-shift events than the pandemic group M clade. We propose that this may be a reflection of the height of the species barrier between gorillas and humans versus chimpanzees and humans. Our results provide a genome-wide view of the constraints operating on proteins of HIV-1 and SIV.

scholarly journals Gorilla APOBEC3 restricts SIVcpz and influences lentiviral evolution in great ape cross-species transmissions

2018 ◽  
Author(s):  
Yusuke Nakano ◽  
Keisuke Yamamoto ◽  
Andrew Soper ◽  
Ryuichi Kumata ◽  
Hirofumi Aso ◽  
...  
Keyword(s):  
List Type ◽  
Great Ape ◽  
Restriction Factors ◽  
Species Barrier ◽  
New Host ◽  
Antiviral Effects ◽  
Apobec3 Family ◽  
Vif Protein ◽  
Hiv 1 ◽  
New Host Species

SummaryRestriction factors including APOBEC3 family proteins have the potential prevent cross-species lentivirus transmissions. Such events as well as ensuing pathogenesis require the viral Vif protein to overcome/neutralize/degrade the APOBEC3 enzymes of the new host species. Previous investigations have focused on the molecular interaction between human APOBEC3s and HIV-1 Vif. However, the evolutionary interplay between lentiviruses and great ape (including human, chimpanzee and gorilla) APOBEC3s has not been fully investigated. Here we demonstrate that gorilla APOBEC3G plays a pivotal role in restricting lentiviral transmission from chimpanzee to gorilla. We also reveal that a sole amino acid substitution in Vif is sufficient to overcome the gorilla APOBEC3G-mediated species barrier. Moreover, the antiviral effects of gorilla APOBEC3D and APOBEC3F are considerably weaker than those of human and chimpanzee counterparts, which can result in the skewed evolution of great ape lentiviruses leading to HIV-1.HighlightsSIVcpz requires M16E mutation in Vif to counteract gorilla A3GAcidic residue at position 16 of Vif is crucial to counteract gorilla A3GGorilla A3D and A3F poorly suppress lentiviral infectivitySIVgor and related HIV-1s counteract human A3D and A3F independently of DRMR motif

scholarly journals High Natural Permissivity of Primary Rabbit Cells for HIV-1, with a Virion Infectivity Defect in Macrophages as the Final Replication Barrier

2010 ◽  
Vol 84 (23) ◽  
pp. 12300-12314 ◽  
Author(s):  
Hanna-Mari Tervo ◽  
Oliver T. Keppler
Keyword(s):  
T Cells ◽  
Late Phase ◽  
Small Animal ◽  
Receptor Complex ◽  
Restriction Factors ◽  
Cyclin T1 ◽  
Primary Rabbit ◽  
Species Specific ◽  
Hiv 1

ABSTRACT An immunocompetent, permissive, small-animal model would be valuable for the study of human immunodeficiency virus type 1 (HIV-1) pathogenesis and for the testing of drug and vaccine candidates. However, the development of such a model has been hampered by the inability of primary rodent cells to efficiently support several steps of the HIV-1 replication cycle. Although transgenesis of the HIV receptor complex and human cyclin T1 have been beneficial, additional late-phase blocks prevent robust replication of HIV-1 in rodents and limit the range of in vivo applications. In this study, we explored the HIV-1 susceptibility of rabbit primary T cells and macrophages. Envelope-specific and coreceptor-dependent entry of HIV-1 was achieved by expressing human CD4 and CCR5. A block of HIV-1 DNA synthesis, likely mediated by TRIM5, was overcome by limited changes to the HIV-1 gag gene. Unlike with mice and rats, primary cells from rabbits supported the functions of the regulatory viral proteins Tat and Rev, Gag processing, and the release of HIV-1 particles at levels comparable to those in human cells. While HIV-1 produced by rabbit T cells was highly infectious, a macrophage-specific infectivity defect became manifest by a complex pattern of mutations in the viral genome, only part of which were deamination dependent. These results demonstrate a considerable natural HIV-1 permissivity of the rabbit species and suggest that receptor complex transgenesis combined with modifications in gag and possibly vif of HIV-1 to evade species-specific restriction factors might render lagomorphs fully permissive to infection by this pathogenic human lentivirus.

scholarly journals Derivation of simian tropic HIV-1 infectious clone reveals virus adaptation to a new host

2019 ◽  
Vol 116 (21) ◽  
pp. 10504-10509 ◽  
Author(s):  
Fabian Schmidt ◽  
Brandon F. Keele ◽  
Gregory Q. Del Prete ◽  
Dennis Voronin ◽  
Christine M. Fennessey ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Infectious Clone ◽  
Host Protein ◽  
Peripheral Blood Mononuclear ◽  
New Host ◽  
Species Specific ◽  
Hiv 1 ◽  
Pigtail Macaques

To replicate in a new host, lentiviruses must adapt to exploit required host factors and evade species-specific antiviral proteins. Understanding how host protein variation drives lentivirus adaptation allowed us to expand the host range of HIV-1 to pigtail macaques. We have previously derived a viral swarm (in the blood of infected animals) that can cause AIDS in this new host. To further exploit this reagent, we generated infectious molecular clones (IMCs) from the viral swarm. We identified clones with high replicative capacity in pigtail peripheral blood mononuclear cells (PBMC) in vitro and used in vivo replication to select an individual IMC, named stHIV-A19 (for simian tropic HIV-1 clone A19), which recapitulated the phenotype obtained with the viral swarm. Adaptation of HIV-1 in macaques led to the acquisition of amino acid changes in viral proteins, such as capsid (CA), that are rarely seen in HIV-1–infected humans. Using stHIV-A19, we show that these CA changes confer a partial resistance to the host cell inhibitor Mx2 from pigtail macaques, but that complete resistance is associated with a fitness defect. Adaptation of HIV-1 to a new host will lead to a more accurate animal model and a better understanding of virus–host interactions.

scholarly journals TRIM5 and the Regulation of HIV-1 Infectivity

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jeremy Luban
Keyword(s):  
Innate Immune ◽  
Target Cells ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Innate Immune Signaling ◽  
Ubiquitin Ligase Activity ◽  
Species Specific ◽  
Anti Hiv ◽  
Hiv 1

The past ten years have seen an explosion of information concerning host restriction factors that inhibit the replication of HIV-1 and other retroviruses. Among these factors is TRIM5, an innate immune signaling molecule that recognizes the capsid lattice as soon as the retrovirion core is released into the cytoplasm of otherwise susceptible target cells. Recognition of the capsid lattice has several consequences that include multimerization of TRIM5 into a complementary lattice, premature uncoating of the virion core, and activation of TRIM5 E3 ubiquitin ligase activity. Unattached, K63-linked ubiquitin chains are generated that activate the TAK1 kinase complex and downstream inflammatory mediators. Polymorphisms in the capsid recognition domain of TRIM5 explain the observed species-specific differences among orthologues and the relatively weak anti-HIV-1 activity of human TRIM5. Better understanding of the complex interaction between TRIM5 and the retrovirus capsid lattice may someday lead to exploitation of this interaction for the development of potent HIV-1 inhibitors.

scholarly journals Vif of Feline Immunodeficiency Virus from Domestic Cats Protects against APOBEC3 Restriction Factors from Many Felids

2010 ◽  
Vol 84 (14) ◽  
pp. 7312-7324 ◽  
Author(s):  
Jörg Zielonka ◽  
Daniela Marino ◽  
Henning Hofmann ◽  
Naoya Yuhki ◽  
Martin Löchelt ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Domestic Cat ◽  
Moderate Degree ◽  
Restriction Factors ◽  
Cytidine Deaminases ◽  
Immunodeficiency Virus ◽  
Specific Restriction ◽  
Species Specific ◽  
Vif Protein ◽  
Hiv 1

ABSTRACT To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Δvif FIV, felid A3Z2s did not show any antiviral activity against Δvif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether VifFIV can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.VifFIV was constructed. This HIV-1.VifFIV was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor.

scholarly journals The Expression Level of HIV-1 Vif Is Optimized by Nucleotide Changes in the Genomic SA1D2prox Region during the Viral Adaptation Process

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2079
Author(s):  
Takaaki Koma ◽  
Naoya Doi ◽  
Mai Takemoto ◽  
Kyosuke Watanabe ◽  
Hideki Yamamoto ◽  
...  
Keyword(s):  
Viral Genome ◽  
Expression Level ◽  
Restriction Factors ◽  
Single Nucleotide ◽  
Expression Levels ◽  
Naturally Occurring ◽  
Viral Adaptation ◽  
Splicing Pattern ◽  
Apobec3 Proteins ◽  
Hiv 1

HIV-1 Vif plays an essential role in viral replication by antagonizing anti-viral cellular restriction factors, a family of APOBEC3 proteins. We have previously shown that naturally-occurring single-nucleotide mutations in the SA1D2prox region, which surrounds the splicing acceptor 1 and splicing donor 2 sites of the HIV-1 genome, dramatically alter the Vif expression level, resulting in variants with low or excessive Vif expression. In this study, we investigated how these HIV-1 variants with poor replication ability adapt and evolve under the pressure of APOBEC3 proteins. Adapted clones obtained through adaptation experiments exhibited an altered replication ability and Vif expression level compared to each parental clone. While various mutations were present throughout the viral genome, all replication-competent adapted clones with altered Vif expression levels were found to bear them within SA1D2prox, without exception. Indeed, the mutations identified within SA1D2prox were responsible for changes in the Vif expression levels and altered the splicing pattern. Moreover, for samples collected from HIV-1-infected patients, we showed that the nucleotide sequences of SA1D2prox can be chronologically changed and concomitantly affect the Vif expression levels. Taken together, these results demonstrated the importance of the SA1D2prox nucleotide sequence for modulating the Vif expression level during HIV-1 replication and adaptation.

scholarly journals Influence of gag on Human Immunodeficiency Virus Type 1 Species-Specific Tropism

2004 ◽  
Vol 78 (21) ◽  
pp. 11816-11822 ◽  
Author(s):  
Yasuhiro Ikeda ◽  
Laura M. J. Ylinen ◽  
Maria Kahar-Bador ◽  
Greg J. Towers
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Restriction Factors ◽  
Narrow Host Range ◽  
Immunodeficiency Virus ◽  
Lentiviral Infection ◽  
Species Specific ◽  
Hiv 1

ABSTRACT The narrow host range of human immunodeficiency virus type 1 (HIV-1) is due in part to dominant acting restriction factors in humans (Ref1) and monkeys (Lv1). Here we show that gag encodes determinants of species-specific lentiviral infection, related in part to such restriction factors. Interaction between capsid and host cyclophilin A (CypA) protects HIV-1 from restriction in human cells but is essential for maximal restriction in simian cells. We show that sequence variation between HIV-1 isolates leads to variation in sensitivity to restriction factors in human and simian cells. We present further evidence for the importance of target cell CypA over CypA packaged in virions, specifically in the context of gp160 pseudotyped HIV-1 vectors. We also show that sensitivity to restriction is controlled by an H87Q mutation in the capsid, implicated in the immune control of HIV-1, possibly linking immune and innate control of HIV-1 infection.

Restriction Factors in HIV-1 Disease Progression

2015 ◽  
Vol 13 (6) ◽  
pp. 448-461 ◽  
Author(s):  
Natacha Merindol ◽  
Lionel Berthoux
Keyword(s):  
Disease Progression ◽  
Restriction Factors ◽  
Hiv 1

scholarly journals An evolutionary genomic approach reveals both conserved and species-specific genetic elements related to human disease in closely related Aspergillus fungi

Genetics ◽  
2021 ◽  
Author(s):  
Matthew E Mead ◽  
Jacob L Steenwyk ◽  
Lilian P Silva ◽  
Patrícia A de Castro ◽  
Nauman Saeed ◽  
...  
Keyword(s):  
Human Disease ◽  
Evolutionary Rate ◽  
Fungal Disease ◽  
Comparative Genomic ◽  
Genetic Elements ◽  
Genomic Approach ◽  
Evolutionary Genomic ◽  
Repeated Evolution ◽  
Species Specific ◽  
Encoding Genes

Abstract Aspergillosis is an important opportunistic human disease caused by filamentous fungi in the genus Aspergillus. Roughly 70% of infections are caused by Aspergillus fumigatus, with the rest stemming from approximately a dozen other Aspergillus species. Several of these pathogens are closely related to A. fumigatus and belong in the same taxonomic section, section Fumigati. Pathogenic species are frequently most closely related to non-pathogenic ones, suggesting Aspergillus pathogenicity evolved multiple times independently. To understand the repeated evolution of Aspergillus pathogenicity, we performed comparative genomic analyses on 18 strains from 13 species, including 8 species in section Fumigati, which aimed to identify genes, both ones previously connected to virulence as well as ones never before implicated, whose evolution differs between pathogens and non-pathogens. We found that most genes were present in all species, including approximately half of those previously connected to virulence, but a few genes were section- or species-specific. Evolutionary rate analyses identified over 1,700 genes whose evolutionary rate differed between pathogens and non-pathogens and dozens of genes whose rates differed between specific pathogens and the rest of the taxa. Functional testing of deletion mutants of 17 transcription factor-encoding genes whose evolution differed between pathogens and non-pathogens identified eight genes that affect either fungal survival in a model of phagocytic killing, host survival in an animal model of fungal disease, or both. These results suggest that the evolution of pathogenicity in Aspergillus involved both conserved and species-specific genetic elements, illustrating how an evolutionary genomic approach informs the study of fungal disease.

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