Natural APOBEC3C variants can elicit differential HIV-1 restriction activity.


BACKGROUND:The APOBEC3 (A3) family of DNA cytosine deaminases provides an innate barrier to infection by retroviruses including HIV-1. A total of five enzymes, A3C, A3D, A3F, A3G and A3H, are degraded by the viral accessory protein Vif and expressed at high levels in CD4+ T cells, the primary reservoir for HIV-1 replication in vivo. Apart from A3C, all of these enzymes mediate restriction of Vif-deficient HIV-1. However, a rare variant of human A3C (Ile188) was shown recently to restrict Vif-deficient HIV-1 in a 293T-based single cycle infection system. The potential activity of this naturally occurring A3C variant has yet to be characterized in a T cell-based spreading infection system. Here we employ a combination of Cas9/gRNA disruption and transient and stable protein expression to assess the roles of major Ser188 and minor Ile188 A3C variants in HIV-1 restriction in T cell lines. RESULTS:Cas9-mediated mutation of endogenous A3C in the non-permissive CEM2n T cell line did not alter HIV-1 replication kinetics, and complementation with A3C-Ser188 or A3C-Ile188 was similarly aphenotypic. Stable expression of A3C-Ser188 in the permissive T cell line SupT11 also had little effect. However, stable expression of A3C-Ile188 in SupT11 cells inhibited Vif-deficient virus replication and inflicted G-to-A mutations. CONCLUSIONS:A3C-Ile188 is capable of inhibiting Vif-deficient HIV-1 replication in T cells. Although A3C is eclipsed by the dominant anti-viral activities of other A3s in non-permissive T cell lines and primary T lymphocytes, this enzyme may still be able to contribute to HIV-1 diversification in vivo. Our results highlight the functional redundancy in the human A3 family with regards to HIV-1 restriction and the need to consider naturally occurring variants.






Anderson BD,Ikeda T,Moghadasi SA,Martin AS,Brown WL,Harris RS




Has Abstract


2018-12-17 00:00:00












  • Good CoP, bad CoP? Interrogating the immune responses to primate lentiviral vaccines.

    abstract::Correlates of protection (CoPs) against infection by primate lentiviruses remain undefined. Modest protection against HIV-1 was observed in one human vaccine trial, whereas previous trials and vaccine-challenge experiments in non-human primates have yielded inconsistent but intriguing results. Although high levels of ...


    pub_type: 杂志文章,评审


    authors: Klasse PJ,Moore JP

    更新日期:2012-10-01 00:00:00

  • The silent defense: micro-RNA directed defense against HIV-1 replication.

    abstract::MicroRNAs play critical role in regulating gene expression. MicroRNA profile of particular cell type bears the signature of cell type specific gene expression. Given that viral pathogens replicate by evading host defenses, research is now focused on the miRNA-regulated genes that critically regulate HIV-1 propagation ...


    pub_type: 杂志文章


    authors: Kumar A

    更新日期:2007-04-12 00:00:00

  • Enhanced antibody-mediated neutralization of HIV-1 variants that are resistant to fusion inhibitors.

    abstract:BACKGROUND:HIV-1 typically develops resistance to any single antiretroviral agent. Combined anti-retroviral therapy to reduce drug-resistance development is necessary to control HIV-1 infection. Here, to assess the utility of a combination of antibody and fusion inhibitor treatments, we investigated the potency of mono...


    pub_type: 杂志文章


    authors: Alam M,Kuwata T,Shimura K,Yokoyama M,Ramirez Valdez KP,Tanaka K,Maruta Y,Oishi S,Fujii N,Sato H,Matsuoka M,Matsushita S

    更新日期:2016-09-27 00:00:00

  • Functional analysis of human T lymphotropic virus type 2 Tax proteins.

    abstract:BACKGROUND:The Tax proteins encoded by human T lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) are transcriptional activators of both the viral long terminal repeat (LTR) and cellular promoters via the CREB and NFkB pathways. In contrast to HTLV-1, HTLV-2 has been classified into four distinct genetic subtypes A...


    pub_type: 杂志文章


    authors: Sheehy N,Lillis L,Watters K,Lewis M,Gautier V,Hall W

    更新日期:2006-03-21 00:00:00

  • A purine-rich element in foamy virus pol regulates env splicing and gag/pol expression.

    abstract:BACKGROUND:The foamy viral genome encodes four central purine-rich elements localized in the integrase-coding region of pol. Previously, we have shown that the first two of these RNA elements (A and B) are required for protease dimerization and activation. The D element functions as internal polypurine tract during rev...


    pub_type: 杂志文章


    authors: Moschall R,Denk S,Erkelenz S,Schenk C,Schaal H,Bodem J

    更新日期:2017-02-06 00:00:00

  • Friend retrovirus infection induces the development of memory-like natural killer cells.

    abstract::Traditionally, NK cells belong to the innate immune system and eliminate virus-infected cells through their germline-encoded receptors. However, NK cells were recently reported to possess memory-like functions that were predominantly provided by hepatic NK cells. Memory properties were mainly documented in contact hyp...


    pub_type: 杂志文章


    authors: Littwitz-Salomon E,Nguyen T,Schimmer S,Dittmer U

    更新日期:2018-10-06 00:00:00

  • Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques.

    abstract:BACKGROUND:Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful antiretroviral therapy (ART) in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can b...


    pub_type: 杂志文章


    authors: Metzner KJ,Binley JM,Gettie A,Marx P,Nixon DF,Connor RI

    更新日期:2006-12-21 00:00:00

  • Avian myeoloblastosis virus (AMV): only one side of the coin.

    abstract::For many years, scientists and suppliers have refered to AMV-RT as the reverse transcriptase produced by the Avian Myelobalstosis Virus. This manuscript briefly reviews the molecular basis for biological dependence of AMV for the envelope and RT proteins that are produced by its natural helper the Myeloblastosis Assoc...


    pub_type: 杂志文章,评审


    authors: Perbal B

    更新日期:2008-06-16 00:00:00

  • Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen.

    abstract:BACKGROUND:HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoti...


    pub_type: 杂志文章


    authors: Trible RP,Narute P,Emert-Sedlak LA,Alvarado JJ,Atkins K,Thomas L,Kodama T,Yanamala N,Korotchenko V,Day BW,Thomas G,Smithgall TE

    更新日期:2013-11-14 00:00:00

  • The XVI International Conference on AIDS: the place to be!

    abstract::This editorial represents a plea to retrovirologists to attend the XVI International Conference on AIDS that will take place in Toronto, Canada between August 13-18, 2006. In short, it is vital that politicians and opinion leaders understand that basic scientists are no less committed to the worldwide battle against H...


    pub_type: 社论


    authors: Wainberg MA

    更新日期:2006-02-03 00:00:00

  • Virus-producing cells determine the host protein profiles of HIV-1 virion cores.

    abstract:BACKGROUND:Upon HIV entry into target cells, viral cores are released and rearranged into reverse transcription complexes (RTCs), which support reverse transcription and also protect and transport viral cDNA to the site of integration. RTCs are composed of viral and cellular proteins that originate from both target and...


    pub_type: 杂志文章


    authors: Santos S,Obukhov Y,Nekhai S,Bukrinsky M,Iordanskiy S

    更新日期:2012-08-13 00:00:00

  • Perinatal HIV-1 transmission: Fc gamma receptor variability associates with maternal infectiousness and infant susceptibility.

    abstract:BACKGROUND:Accumulating data suggest that immune effector functions mediated through the Fc portion of HIV-1-specific immunoglobulin G (IgG) are a key component of HIV-1 protective immunity, affecting both disease progression and HIV-1 acquisition. Through studying Fc gamma receptor (FcγR) variants known to alter IgG F...


    pub_type: 杂志文章


    authors: Lassaunière R,Musekiwa A,Gray GE,Kuhn L,Tiemessen CT

    更新日期:2016-06-10 00:00:00

  • Higher levels of Zidovudine resistant HIV in the colon compared to blood and other gastrointestinal compartments in HIV infection.

    abstract:BACKGROUND:The gut-associated lymphoid tissue (GALT) is the largest lymphoid organ infected by human immunodeficiency virus type 1 (HIV-1). It serves as a viral reservoir and host-pathogen interface in infection. This study examined whether different parts of the gut and peripheral blood lymphocytes (PBL) contain diffe...


    pub_type: 杂志文章


    authors: van Marle G,Church DL,Nunweiler KD,Cannon K,Wainberg MA,Gill MJ

    更新日期:2010-09-13 00:00:00

  • Induction of p21(CIP1/WAF1) expression by human T-lymphotropic virus type 1 Tax requires transcriptional activation and mRNA stabilization.

    abstract::HTLV-1 Tax can induce senescence by up-regulating the levels of cyclin-dependent kinase inhibitors p21(CIP1/WAF1) and p27(KIP1). Tax increases p27(KIP1) protein stability by activating the anaphase promoting complex/cyclosome (APC/C) precociously, causing degradation of Skp2 and inactivation of SCF(Skp2), the E3 ligas...


    pub_type: 杂志文章


    authors: Zhang L,Zhi H,Liu M,Kuo YL,Giam CZ

    更新日期:2009-04-08 00:00:00

  • HIV-1 Rev oligomerization is not obligatory in the presence of an extra basic domain.

    abstract:BACKGROUND:The HIV-1 Rev regulatory protein binds as an oligomeric complex to viral RNA mediating nuclear export of incompletely spliced and non-spliced viral mRNAs encoding the viral structural proteins. However, the biological significance of the obligatory complex formation of Rev upon the viral RNA is unclear. RES...


    pub_type: 杂志文章


    authors: Furnes C,Arnesen T,Askjaer P,Kjems J,Szilvay AM

    更新日期:2005-06-10 00:00:00

  • Expression of infectious murine leukemia viruses by RAW264.7 cells, a potential complication for studies with a widely used mouse macrophage cell line.

    abstract::The mouse macrophage-like cell line RAW264.7, the most commonly used mouse macrophage cell line in medical research, was originally reported to be free of replication-competent murine leukemia virus (MuLV) despite its origin in a tumor induced by Abelson MuLV containing Moloney MuLV as helper virus. As currently avail...


    pub_type: 杂志文章


    authors: Hartley JW,Evans LH,Green KY,Naghashfar Z,Macias AR,Zerfas PM,Ward JM

    更新日期:2008-01-04 00:00:00

  • The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil.

    abstract::HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in th...


    pub_type: 杂志文章,评审


    authors: Ishak R,de Oliveira Guimarães Ishak M,Vallinoto ACR

    更新日期:2020-02-14 00:00:00

  • Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses.

    abstract::Efforts to assess the prevalence of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and chronic fatigue syndrome have relied heavily on PCR-based testing of clinical samples and have yielded widely divergent findings. This week in Retrovirology, reports from four independent rese...


    pub_type: 杂志文章


    authors: Smith RA

    更新日期:2010-12-20 00:00:00

  • H-index, mentoring-index, highly-cited and highly-accessed: how to evaluate scientists?

    abstract::How best to evaluate scientists within a peer group is a difficult task. This editorial discusses the use of the H-index and total citations. It also raises the consideration of a mentoring-index and the value of understanding the frequency that a published paper is accessed by readers. ...


    pub_type: 社论


    authors: Jeang KT

    更新日期:2008-11-25 00:00:00

  • Limited cross-border infections in patients newly diagnosed with HIV in Europe.

    abstract:BACKGROUND:International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patie...


    pub_type: 杂志文章


    authors: Frentz D,Wensing AM,Albert J,Paraskevis D,Abecasis AB,Hamouda O,Jørgensen LB,Kücherer C,Struck D,Schmit JC,Åsjö B,Balotta C,Beshkov D,Camacho RJ,Clotet B,Coughlan S,De Wit S,Griskevicius A,Grossman Z,Horban A,Kolu

    更新日期:2013-04-03 00:00:00

  • SAMHD1 restricts HIV-1 infection in dendritic cells (DCs) by dNTP depletion, but its expression in DCs and primary CD4+ T-lymphocytes cannot be upregulated by interferons.

    abstract:BACKGROUND:SAMHD1 is an HIV-1 restriction factor in non-dividing monocytes, dendritic cells (DCs), macrophages, and resting CD4+ T-cells. Acting as a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, SAMHD1 hydrolyzes dNTPs and restricts HIV-1 infection in macrophages and resting CD4+ T-cells by decreasing the i...


    pub_type: 杂志文章


    authors: St Gelais C,de Silva S,Amie SM,Coleman CM,Hoy H,Hollenbaugh JA,Kim B,Wu L

    更新日期:2012-12-11 00:00:00

  • Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal.

    abstract:BACKGROUND:We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus ...


    pub_type: 杂志文章


    authors: Van Rompay KK,Trott KA,Jayashankar K,Geng Y,LaBranche CC,Johnson JA,Landucci G,Lipscomb J,Tarara RP,Canfield DR,Heneine W,Forthal DN,Montefiori D,Abel K

    更新日期:2012-07-17 00:00:00

  • OVEX1, a novel chicken endogenous retrovirus with sex-specific and left-right asymmetrical expression in gonads.

    abstract:BACKGROUND:In chickens, as in most birds, female gonad morphogenesis is asymmetrical. Gonads appear first rather similarly, but only the left one undergoes full differentiation and gives rise to a functional ovary. The right gonad, in which the cortex does not develop, remains restricted to the medulla and finally regr...


    pub_type: 杂志文章


    authors: Carré-Eusèbe D,Coudouel N,Magre S

    更新日期:2009-06-17 00:00:00

  • HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms.

    abstract::The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. In this study, we examined the basis of resistance of HIV-1 clade C Envs obtained from broadly cross neutralizing (BCN) plasma of an Indian donor with N332...


    pub_type: 杂志文章


    authors: Deshpande S,Patil S,Kumar R,Hermanus T,Murugavel KG,Srikrishnan AK,Solomon S,Morris L,Bhattacharya J

    更新日期:2016-08-30 00:00:00

  • Inactivation of HIV-1 in breast milk by treatment with the alkyl sulfate microbicide sodium dodecyl sulfate (SDS).

    abstract:BACKGROUND:Reducing transmission of HIV-1 through breast milk is needed to help decrease the burden of pediatric HIV/AIDS in society. We have previously reported that alkyl sulfates (i.e., sodium dodecyl sulfate, SDS) are microbicidal against HIV-1 at low concentrations, are biodegradable, have little/no toxicity and a...


    pub_type: 杂志文章


    authors: Urdaneta S,Wigdahl B,Neely EB,Berlin CM Jr,Schengrund CL,Lin HM,Howett MK

    更新日期:2005-04-29 00:00:00

  • Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase.

    abstract:BACKGROUND:The 18 residue tail abutting the SH3 fold that comprises the heart of the C-terminal domain is the only part of HIV-1 integrase yet to be visualized by structural biology. To ascertain the role of the tail region in integrase function and HIV-1 replication, a set of deletion mutants that successively lacked ...


    pub_type: 杂志文章


    authors: Dar MJ,Monel B,Krishnan L,Shun MC,Di Nunzio F,Helland DE,Engelman A

    更新日期:2009-10-19 00:00:00

  • Multiple independent origins of a protease inhibitor resistance mutation in salvage therapy patients.

    abstract:BACKGROUND:Combination anti-viral therapies have reduced treatment failure rates by requiring multiple specific mutations to be selected on the same viral genome to impart high-level drug resistance. To determine if the common protease inhibitor resistance mutation L90M is only selected once or repeatedly on different ...


    pub_type: 杂志文章


    authors: Kapoor A,Shapiro B,Shafer RW,Shulman N,Rhee SY,Delwart EL

    更新日期:2008-01-25 00:00:00

  • Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells.

    abstract:BACKGROUND:All human immunodeficiency virus (HIV-1) uses a host tRNALys,3 as the primer for reverse transcription. The tRNALys,3 is bound to a region on the HIV-1 genome, the primer-binding site (PBS), that is complementary to the 18 terminal nucleotides of tRNALys,3. How HIV-1 selects the tRNA from the intracellular m...


    pub_type: 杂志文章


    authors: Moore-Rigdon KL,Kosloff BR,Kirkman RL,Morrow CD

    更新日期:2005-03-24 00:00:00

  • Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies peroxisome proliferator-activated receptor gamma as an intrinsic negative regulator of viral replication.

    abstract:BACKGROUND:We previously demonstrated that primary Th1Th17 cells are highly permissive to HIV-1, whereas Th1 cells are relatively resistant. Molecular mechanisms underlying these differences remain unknown. RESULTS:Exposure to replication competent and single-round VSV-G pseudotyped HIV strains provide evidence that s...


    pub_type: 杂志文章


    authors: Bernier A,Cleret-Buhot A,Zhang Y,Goulet JP,Monteiro P,Gosselin A,DaFonseca S,Wacleche VS,Jenabian MA,Routy JP,Tremblay C,Ancuta P

    更新日期:2013-12-21 00:00:00

  • Microbial exposure alters HIV-1-induced mucosal CD4+ T cell death pathways Ex vivo.

    abstract:BACKGROUND:Early HIV-1 infection causes massive CD4+ T cell death in the gut and translocation of bacteria into the circulation. However, the programmed cell death (PCD) pathways used by HIV-1 to kill CD4+ T cells in the gut, and the impact of microbial exposure on T cell loss, remain unclear. Understanding mucosal HIV...


    pub_type: 杂志文章


    authors: Steele AK,Lee EJ,Manuzak JA,Dillon SM,Beckham JD,McCarter MD,Santiago ML,Wilson CC

    更新日期:2014-02-04 00:00:00