Host gene evolution traces the evolutionary history of ancient primate lentiviruses

Compton, Alex A.; Malik, Harmit S.; Emerman, Michael

doi:10.1098/rstb.2012.0496

Cited by 70 publications

(65 citation statements)

References 78 publications

(109 reference statements)

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“…The simian immunodeficiency virus, for instance, can be traced back more than 10 million years (Compton et al, 2013) while retroviral orthologues predating the divergence of placental mammals exceed 100 million years (Lee et al, 2013). The downside is that host defense mechanisms are equally mature and can result in pronounced immune reactions in addition to innate restriction at the post-entry level (Kajaste-Rudnitski and Naldini, 2015).…”

Section: Established Methods Of Ocular Gene Therapymentioning

confidence: 99%

Gene transfer to the outflow tract

Dang

Loewen

Parikh

et al. 2017

Experimental Eye Research

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Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15 to 20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-β and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm's canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

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Section: Established Methods Of Ocular Gene Therapymentioning

confidence: 99%

Gene transfer to the outflow tract

Dang

Loewen

Parikh

et al. 2017

Experimental Eye Research

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“…2B) (Lim et al, 2012). Similarly, using episodic positive selection as an evolutionary echo of a previous infection has allowed more accurate dating of the origin of lentiviruses (Compton et al, 2013) and hepaciviruses (Patel et al, 2012). Such dating would be imprecise using only sequences of the viruses because their rapid evolution leads to an under-estimation of viral age, often by several orders of magnitude (Holmes, 2008;Patel et al, 2011;Wertheim and Worobey, 2009).…”

Section: When?mentioning

confidence: 99%

Genetic conflicts: the usual suspects and beyond

McLaughlin

Malik

2017

Journal of Experimental Biology

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137

127

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Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter-adaptation, commonly referred to as Red Queen interactions. In this review, we explore insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). We argue that many different characteristics of selfish genetic elements can be distilled into two types of advantages: an overreplication advantage (e.g. mobile genetic elements in genomes) and a transmission distortion advantage (e.g. meiotic drivers in populations). These two general categories may help classify disparate types of selfish genetic elements.

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“…Unlike APOBEC3-Vif1 interactions, very few studies have attempted to define the interactions between HIV-2 Vif (Vif2) and the APOBEC3 proteins (11,13). There is only ϳ30% amino acid identity between Vif1 from NL4-3 and Vif2 from HIV-2 ROD12 .…”

mentioning

confidence: 99%

“…Members of the human apolipoprotein B mRNAediting enzyme catalytic polypeptide-like 3 (APOBEC3 [A3]) family of proteins are potent cellular restriction factors that provide a defense against viral infection by incorporating into virions and targeting nascent viral DNA for deamination of cytidine residues to uridines (1)(2)(3)(4)(5)(6)(7)(8); cytidine deamination of the viral DNA leads to lethal hypermutation of the targeted virus. However, both HIV-1 and HIV-2 have accessory proteins, called viral infectivity factors (Vifs), that can bind to the APOBEC3 proteins to promote their ubiquitination and subsequent proteosomal degradation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18), thereby suppressing their virion incorporation.…”

mentioning

confidence: 99%

HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants

Smith

Izumi

Borbet

et al. 2014

J Virol

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Human APOBEC3 (A3) restriction factors provide intrinsic immunity against zoonotic transmission of pathogenic viruses. A3D, A3F, A3G, and A3H haplotype II (A3H-hapII) can be packaged into virion infectivity factor (Vif)-deficient HIVs to inhibit viral replication. To overcome these restriction factors, Vif binds to the A3 proteins in viral producer cells to target them for ubiquitination and proteasomal degradation, thus preventing their packaging into assembling virions. Therefore, the Vif-A3 interactions are attractive targets for novel drug development. HIV-1 and HIV-2 arose via distinct zoonotic transmission events of simian immunodeficiency viruses from chimpanzees and sooty mangabeys, respectively, and Vifs from these viruses have limited homology. To gain insights into the evolution of virus-host interactions that led to successful cross-species transmission of lentiviruses, we characterized the determinants of the interaction between HIV-2 Vif (Vif2) with human A3 proteins and compared them to the previously identified HIV-1 Vif (Vif1) interactions with the A3 proteins. We found that A3G, A3F, and A3H-hapII, but not A3D, were susceptible to Vif2-induced degradation. Alanine-scanning mutational analysis of the first 62 amino acids of Vif2 indicated that Vif2 determinants important for degradation of A3G and A3F are completely distinct from these regions in Vif1, as are the determinants in A3G and A3F that are critical for Vif2-induced degradation. These observations suggest that distinct Vif-A3 interactions evolved independently in different SIVs and their nonhuman primate hosts and conservation of the A3 determinants targeted by the SIV Vif proteins resulted in successful zoonotic transmission into humans. IMPORTANCEPrimate APOBEC3 proteins provide innate immunity against invading pathogens, and Vif proteins of primate lentiviruses have evolved to overcome these host defenses by interacting with them and inducing their proteasomal degradation. HIV-1 and HIV-2 are two human pathogens that induce AIDS, and elucidating interactions between their Vif proteins and human A3 proteins could facilitate the development of novel antiviral drugs. Furthermore, understanding Vif-A3 interactions can provide novel insights into the cross-species transmission events that led to the HIV-1 and HIV-2 pandemics and evolution of host-virus interactions. We carried out mutational analysis of the N-terminal 62 amino acids of HIV-2 Vif (Vif2) and analyzed A3G/A3F chimeras that retained antiviral activity to identify the determinants of the Vif2 and A3 interaction. Our results show that the Vif2-A3 interactions are completely different from the Vif1-A3 interactions, suggesting that these interactions evolved independently and that conservation of the A3 determinants resulted in successful zoonotic transmission into humans.

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Host gene evolution traces the evolutionary history of ancient primate lentiviruses

Cited by 70 publications

References 78 publications

Gene transfer to the outflow tract

Gene transfer to the outflow tract

Genetic conflicts: the usual suspects and beyond

HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants

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