HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

Abstract:

:Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001). CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Erdmann N,Du VY,Carlson J,Schaefer M,Jureka A,Sterrett S,Yue L,Dilernia D,Lakhi S,Tang J,Sidney J,Gilmour J,Allen S,Hunter E,Heath S,Bansal A,Goepfert PA

doi

10.1371/journal.ppat.1005111

subject

Has Abstract

pub_date

2015-08-24 00:00:00

pages

e1005111

issue

8

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-15-01316

journal_volume

11

pub_type

杂志文章
  • Competent but complex communication: The phenomena of pheromone-responsive plasmids.

    abstract::Enterococci are robust gram-positive bacteria that are found in a variety of surroundings and that cause a significant number of healthcare-associated infections. The genus possesses a high-efficiency pheromone-responsive plasmid (PRP) transfer system for genetic exchange that allows antimicrobial-resistance determina...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,评审

    doi:10.1371/journal.ppat.1008310

    authors: Sterling AJ,Snelling WJ,Naughton PJ,Ternan NG,Dooley JSG

    更新日期:2020-04-02 00:00:00

  • Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo.

    abstract::Adenoviral vectors have shown significant promise as vaccine delivery vectors due to their ability to elicit both innate and adaptive immune responses. α-defensins are effector molecules of the innate immune response and have been shown to modulate natural infection with adenoviruses, but the majority of α-defensin-ad...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008180

    authors: Tartaglia LJ,Badamchi-Zadeh A,Abbink P,Blass E,Aid M,Gebre MS,Li Z,Pastores KC,Trott S,Gupte S,Larocca RA,Barouch DH

    更新日期:2019-12-16 00:00:00

  • A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    abstract::In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenit...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005755

    authors: Coleman S,Choi KY,Root M,McGregor A

    更新日期:2016-07-07 00:00:00

  • Disruption of PML nuclear bodies is mediated by ORF61 SUMO-interacting motifs and required for varicella-zoster virus pathogenesis in skin.

    abstract::Promyelocytic leukemia protein (PML) has antiviral functions and many viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infe...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002157

    authors: Wang L,Oliver SL,Sommer M,Rajamani J,Reichelt M,Arvin AM

    更新日期:2011-08-01 00:00:00

  • Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.

    abstract::Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate b...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001309

    authors: Ramiro RS,Alpedrinha J,Carter L,Gardner A,Reece SE

    更新日期:2011-03-01 00:00:00

  • Head-to-head comparisons of Toxoplasma gondii and its near relative Hammondia hammondi reveal dramatic differences in the host response and effectors with species-specific functions.

    abstract::Toxoplasma gondii and Hammondia hammondi are closely-related coccidian intracellular parasites that differ in their ability to cause disease in animal and (likely) humans. The role of the host response in these phenotypic differences is not known and to address this we performed a transcriptomic analysis of a monocyte...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008528

    authors: Wong ZS,Sokol-Borrelli SL,Olias P,Dubey JP,Boyle JP

    更新日期:2020-06-23 00:00:00

  • The Legionella pneumophila effector VipA is an actin nucleator that alters host cell organelle trafficking.

    abstract::Legionella pneumophila, the causative agent of Legionnaires' disease, invades and replicates within macrophages and protozoan cells inside a vacuole. The type IVB Icm/Dot secretion system is necessary for the translocation of effector proteins that modulate vesicle trafficking pathways in the host cell, thus avoiding ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002546

    authors: Franco IS,Shohdy N,Shuman HA

    更新日期:2012-02-01 00:00:00

  • Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites.

    abstract::Autophagy is a cellular process that is highly conserved among eukaryotes and permits the degradation of cellular material. Autophagy is involved in multiple survival-promoting processes. It not only facilitates the maintenance of cell homeostasis by degrading long-lived proteins and damaged organelles, but it also pl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002416

    authors: Besteiro S,Brooks CF,Striepen B,Dubremetz JF

    更新日期:2011-12-01 00:00:00

  • Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.

    abstract::Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that persists lifelong in the host. In ∼4% of infected people, HTLV-1 causes a chronic disabling neuroinflammatory disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathogenesis of HAM/TSP is unknown and treatment remain...

    journal_title:PLoS pathogens

    pub_type: 临床试验,杂志文章

    doi:10.1371/journal.ppat.1002480

    authors: Tattermusch S,Skinner JA,Chaussabel D,Banchereau J,Berry MP,McNab FW,O'Garra A,Taylor GP,Bangham CR

    更新日期:2012-01-01 00:00:00

  • Modulation of the Immune Response by Nematode Secreted Acetylcholinesterase Revealed by Heterologous Expression in Trypanosoma musculi.

    abstract::Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural p...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005998

    authors: Vaux R,Schnoeller C,Berkachy R,Roberts LB,Hagen J,Gounaris K,Selkirk ME

    更新日期:2016-11-01 00:00:00

  • Dual miRNA targeting restricts host range and attenuates neurovirulence of flaviviruses.

    abstract::Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenua...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004852

    authors: Tsetsarkin KA,Liu G,Kenney H,Bustos-Arriaga J,Hanson CT,Whitehead SS,Pletnev AG

    更新日期:2015-04-23 00:00:00

  • In vivo administration of a JAK3 inhibitor during acute SIV infection leads to significant increases in viral load during chronic infection.

    abstract::The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003929

    authors: Takahashi Y,Byrareddy SN,Albrecht C,Brameier M,Walter L,Mayne AE,Dunbar P,Russo R,Little DM,Villinger T,Khowawisetsut L,Pattanapanyasat K,Villinger F,Ansari AA

    更新日期:2014-03-06 00:00:00

  • A high-resolution view of genome-wide pneumococcal transformation.

    abstract::Transformation is an important mechanism of microbial evolution through which bacteria have been observed to rapidly adapt in response to clinical interventions; examples include facilitating vaccine evasion and the development of penicillin resistance in the major respiratory pathogen Streptococcus pneumoniae. To cha...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002745

    authors: Croucher NJ,Harris SR,Barquist L,Parkhill J,Bentley SD

    更新日期:2012-01-01 00:00:00

  • Cross-Species Transmission and Differential Fate of an Endogenous Retrovirus in Three Mammal Lineages.

    abstract::Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005279

    authors: Zhuo X,Feschotte C

    更新日期:2015-11-12 00:00:00

  • 14-3-3 scaffold proteins mediate the inactivation of trim25 and inhibition of the type I interferon response by herpesvirus deconjugases.

    abstract::The 14-3-3 molecular scaffolds promote type I interferon (IFN) responses by stabilizing the interaction of RIG-I with the TRIM25 ligase. Viruses have evolved unique strategies to halt this cellular response to support their replication and spread. Here, we report that the ubiquitin deconjugase (DUB) encoded in the N-t...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008146

    authors: Gupta S,Ylä-Anttila P,Sandalova T,Sun R,Achour A,Masucci MG

    更新日期:2019-11-11 00:00:00

  • The plant actin cytoskeleton responds to signals from microbe-associated molecular patterns.

    abstract::Plants are constantly exposed to a large and diverse array of microbes; however, most plants are immune to the majority of potential invaders and susceptible to only a small subset of pathogens. The cytoskeleton comprises a dynamic intracellular framework that responds rapidly to biotic stresses and supports numerous ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003290

    authors: Henty-Ridilla JL,Shimono M,Li J,Chang JH,Day B,Staiger CJ

    更新日期:2013-01-01 00:00:00

  • C. elegans germ cells show temperature and age-dependent expression of Cer1, a Gypsy/Ty3-related retrotransposon.

    abstract::Virus-like particles (VLPs) have not been observed in Caenorhabditis germ cells, although nematode genomes contain low numbers of retrotransposon and retroviral sequences. We used electron microscopy to search for VLPs in various wild strains of Caenorhabditis, and observed very rare candidate VLPs in some strains, in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002591

    authors: Dennis S,Sheth U,Feldman JL,English KA,Priess JR

    更新日期:2012-01-01 00:00:00

  • Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

    abstract::KSHV is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentricCastleman's disease (MCD). The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regula...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002884

    authors: Haecker I,Gay LA,Yang Y,Hu J,Morse AM,McIntyre LM,Renne R

    更新日期:2012-01-01 00:00:00

  • Measles skin rash: Infection of lymphoid and myeloid cells in the dermis precedes viral dissemination to the epidermis.

    abstract::Measles is characterized by fever and a maculopapular skin rash, which is accompanied by immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin biopsies from humans and non-human primates (NHPs) with measles rash have identified MV-infected keratinocytes and mononuclear cells in the ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008253

    authors: Laksono BM,Fortugno P,Nijmeijer BM,de Vries RD,Cordisco S,Kuiken T,Geijtenbeek TBH,Duprex WP,Brancati F,de Swart RL

    更新日期:2020-10-08 00:00:00

  • Ross, macdonald, and a theory for the dynamics and control of mosquito-transmitted pathogens.

    abstract::Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different m...

    journal_title:PLoS pathogens

    pub_type: 传,历史文章,杂志文章

    doi:10.1371/journal.ppat.1002588

    authors: Smith DL,Battle KE,Hay SI,Barker CM,Scott TW,McKenzie FE

    更新日期:2012-01-01 00:00:00

  • A multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma pathogenesis.

    abstract::Endemic Burkitt's lymphoma (eBL) arises from the germinal center (GC). It is a common tumor of young children in tropical Africa and its occurrence is closely linked geographically with the incidence of P. falciparum malaria. This association was noted more than 50 years ago. Since then we have learned that eBL contai...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004170

    authors: Torgbor C,Awuah P,Deitsch K,Kalantari P,Duca KA,Thorley-Lawson DA

    更新日期:2014-05-29 00:00:00

  • Inhibition of competence development, horizontal gene transfer and virulence in Streptococcus pneumoniae by a modified competence stimulating peptide.

    abstract::Competence stimulating peptide (CSP) is a 17-amino acid peptide pheromone secreted by Streptococcus pneumoniae. Upon binding of CSP to its membrane-associated receptor kinase ComD, a cascade of signaling events is initiated, leading to activation of the competence regulon by the response regulator ComE. Genes encoding...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002241

    authors: Zhu L,Lau GW

    更新日期:2011-09-01 00:00:00

  • Hepatitis C Virus Stimulates Murine CD8α-Like Dendritic Cells to Produce Type I Interferon in a TRIF-Dependent Manner.

    abstract::Hepatitis C virus (HCV) induces interferon (IFN) stimulated genes in the liver despite of distinct innate immune evasion mechanisms, suggesting that beyond HCV infected cells other cell types contribute to innate immune activation. Upon coculture with HCV replicating cells, human CD141+ myeloid dendritic cells (DC) pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005736

    authors: Pfaender S,Grabski E,Detje CN,Riebesehl N,Lienenklaus S,Steinmann E,Kalinke U,Pietschmann T

    更新日期:2016-07-06 00:00:00

  • The Activation of Phytophthora Effector Avr3b by Plant Cyclophilin is Required for the Nudix Hydrolase Activity of Avr3b.

    abstract::Plant pathogens secrete an arsenal of effector proteins to impair host immunity. Some effectors possess enzymatic activities that can modify their host targets. Previously, we demonstrated that a Phytophthora sojae RXLR effector Avr3b acts as a Nudix hydrolase when expressed in planta; and this enzymatic activity is r...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005139

    authors: Kong G,Zhao Y,Jing M,Huang J,Yang J,Xia Y,Kong L,Ye W,Xiong Q,Qiao Y,Dong S,Ma W,Wang Y

    更新日期:2015-08-28 00:00:00

  • A point mutation in a herpesvirus polymerase determines neuropathogenicity.

    abstract::Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated wit...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030160

    authors: Goodman LB,Loregian A,Perkins GA,Nugent J,Buckles EL,Mercorelli B,Kydd JH,Palù G,Smith KC,Osterrieder N,Davis-Poynter N

    更新日期:2007-11-01 00:00:00

  • TGF-beta signaling controls embryo development in the parasitic flatworm Schistosoma mansoni.

    abstract::Over 200 million people have, and another 600 million are at risk of contracting, schistosomiasis, one of the major neglected tropical diseases. Transmission of this infection, which is caused by helminth parasites of the genus Schistosoma, depends upon the release of parasite eggs from the human host. However, approx...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030052

    authors: Freitas TC,Jung E,Pearce EJ

    更新日期:2007-04-01 00:00:00

  • The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes.

    abstract::All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004520

    authors: Dawn A,Singh S,More KR,Siddiqui FA,Pachikara N,Ramdani G,Langsley G,Chitnis CE

    更新日期:2014-12-18 00:00:00

  • The secreted peptide PIP1 amplifies immunity through receptor-like kinase 7.

    abstract::In plants, innate immune responses are initiated by plasma membrane-located pattern recognition receptors (PRRs) upon recognition of elicitors, including exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Arabidopsis thaliana produces more than 1000 se...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004331

    authors: Hou S,Wang X,Chen D,Yang X,Wang M,Turrà D,Di Pietro A,Zhang W

    更新日期:2014-09-04 00:00:00

  • Metabolic competition between host and pathogen dictates inflammasome responses to fungal infection.

    abstract::The NLRP3 inflammasome has emerged as a central immune regulator that senses virulence factors expressed by microbial pathogens for triggering inflammation. Inflammation can be harmful and therefore this response must be tightly controlled. The mechanisms by which immune cells, such as macrophages, discriminate benign...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008695

    authors: Tucey TM,Verma J,Olivier FAB,Lo TL,Robertson AAB,Naderer T,Traven A

    更新日期:2020-08-04 00:00:00

  • A role for microRNA-155 modulation in the anti-HIV-1 effects of Toll-like receptor 3 stimulation in macrophages.

    abstract::HIV-1 infection of macrophages plays a key role in viral pathogenesis and progression to AIDS. Polyinosine-polycytidylic acid (poly(I:C); a synthetic analog of dsRNA) and bacterial lipopolysaccharide (LPS), the ligands for Toll-like receptors (TLR) TLR3 and TLR4, respectively, are known to decrease HIV-1 infection in ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002937

    authors: Swaminathan G,Rossi F,Sierra LJ,Gupta A,Navas-Martín S,Martín-García J

    更新日期:2012-09-01 00:00:00