A conformational switch in human immunodeficiency virus gp41 revealed by the structures of overlapping epitopes recognized by neutralizing antibodies.

Abstract:

:The membrane-proximal external region (MPER) of the human immunodeficiency virus (HIV) envelope glycoprotein (gp41) is critical for viral fusion and infectivity and is the target of three of the five known broadly neutralizing HIV type 1 (HIV-1) antibodies, 2F5, Z13, and 4E10. Here, we report the crystal structure of the Fab fragment of Z13e1, an affinity-enhanced variant of monoclonal antibody Z13, in complex with a 12-residue peptide corresponding to the core epitope (W(670)NWFDITN(677)) at 1.8-A resolution. The bound peptide adopts an S-shaped conformation composed of two tandem, perpendicular helical turns. This conformation differs strikingly from the alpha-helical structure adopted by an overlapping MPER peptide bound to 4E10. Z13e1 binds to an elbow in the MPER at the membrane interface, making relatively few interactions with conserved aromatics (Trp672 and Phe673) that are critical for 4E10 recognition. The comparison of the Z13e1 and 4E10 epitope structures reveals a conformational switch such that neutralization can occur by the recognition of the different conformations and faces of the largely amphipathic MPER. The Z13e1 structure provides significant new insights into the dynamic nature of the MPER, which likely is critical for membrane fusion, and it has significant implications for mechanisms of HIV-1 neutralization by MPER antibodies and for the design of HIV-1 immunogens.

journal_name

J Virol

journal_title

Journal of virology

authors

Pejchal R,Gach JS,Brunel FM,Cardoso RM,Stanfield RL,Dawson PE,Burton DR,Zwick MB,Wilson IA

doi

10.1128/JVI.00685-09

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

8451-62

issue

17

eissn

0022-538X

issn

1098-5514

pii

JVI.00685-09

journal_volume

83

pub_type

杂志文章
  • Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro.

    abstract::Cyclosporine (CsA) and its derivatives potently suppress hepatitis C virus (HCV) replication. Recently, CsA-resistant HCV replicons have been identified in vitro. We examined the dependence of the wild-type and CsA-resistant replicons on various cyclophilins for replication. A strong correlation between CsA resistance...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02614-07

    authors: Yang F,Robotham JM,Nelson HB,Irsigler A,Kenworthy R,Tang H

    更新日期:2008-06-01 00:00:00

  • Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection.

    abstract::The human cytomegalovirus (HCMV) tegument protein pp71, encoded by gene UL82, stimulates viral immediate-early (IE) transcription. pp71 interacts with the cellular protein hDaxx at nuclear domain 10 (ND10) sites, resulting in the reversal of hDaxx-mediated repression of viral transcription. We demonstrate that pp71 di...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01215-08

    authors: Lukashchuk V,McFarlane S,Everett RD,Preston CM

    更新日期:2008-12-01 00:00:00

  • Site on the RNA of an avian sarcoma virus at which primer is bound.

    abstract::In vitro transcription of the avian tumor virus RNA by RNA-directed DNA polymerase is initiated on the unique cellular 4S RNA. Previous studies have shown that on the average there is one such RNA primer hydrogen bonded to each viral 35S RNA. The present study confirms that finding and demonstrates that, at least for ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.16.3.553-558.1975

    authors: Taylor JM,Illmensee R

    更新日期:1975-09-01 00:00:00

  • Expansion of human T-cell leukemia virus type 1 (HTLV-1) reservoir in orally infected rats: inverse correlation with HTLV-1-specific cellular immune response.

    abstract::Adult T-cell leukemia (ATL) occurs in a small population of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals. Although the critical risk factor for ATL development is not clear, it has been noted that ATL is incidentally associated with mother-to-child infection, elevated proviral loads, and weakness i...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.77.5.2956-2963.2003

    authors: Hasegawa A,Ohashi T,Hanabuchi S,Kato H,Takemura F,Masuda T,Kannagi M

    更新日期:2003-03-01 00:00:00

  • HSP90 protects the human T-cell leukemia virus type 1 (HTLV-1) tax oncoprotein from proteasomal degradation to support NF-κB activation and HTLV-1 replication.

    abstract::Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 genome encodes the Tax protein that plays essential regulatory roles in HTLV-1 replication and oncogenic transformation of T lymphocytes....

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02006-13

    authors: Gao L,Harhaj EW

    更新日期:2013-12-01 00:00:00

  • Viral protein determinants of Lassa virus entry and release from polarized epithelial cells.

    abstract::The epithelium plays a key role in the spread of Lassa virus. Transmission from rodents to humans occurs mainly via inhalation or ingestion of droplets, dust, or food contaminated with rodent urine. Here, we investigated Lassa virus infection in cultured epithelial cells and subsequent release of progeny viruses. We s...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02240-09

    authors: Schlie K,Maisa A,Freiberg F,Groseth A,Strecker T,Garten W

    更新日期:2010-04-01 00:00:00

  • Role of envelope protein gE endocytosis in the pseudorabies virus life cycle.

    abstract::Several groups have reported that certain herpesvirus envelope proteins do not remain on the surface of cells that express them but rather are internalized by endocytosis in a recycling process. The biological function of membrane protein endocytosis in the virus life cycle remains a matter of speculation and debate. ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.72.6.4571-4579.1998

    authors: Tirabassi RS,Enquist LW

    更新日期:1998-06-01 00:00:00

  • Mutations of polyomavirus VP1 allow in vitro growth in undifferentiated cells and modify in vivo tissue replication specificity.

    abstract::Mutants of polyomavirus with altered host specificities were isolated in undifferentiated C2 myoblast cells (L. Ricci, R. Maione, C. Passananti, A. Felsani, and P. Amati, J. Virol. 66:7153-7158, 1992). The mutations responsible for this phenotype belonged to either of the two classes: a large duplication of the enhanc...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.68.2.1196-1199.1994

    authors: Mezes B,Amati P

    更新日期:1994-02-01 00:00:00

  • Akt/protein kinase B activation by adenovirus vectors contributes to NFkappaB-dependent CXCL10 expression.

    abstract::In gene therapy, the innate immune system is a significant barrier to the effective application of adenovirus (Ad) vectors. In kidney epithelium-derived (REC) cells, serotype 5 Ad vectors induce the expression of the chemokine CXCL10 (IP-10), a response that is dependent on NFkappaB. Compared to the parental vector Ad...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.23.14507-14515.2005

    authors: Liu Q,White LR,Clark SA,Heffner DJ,Winston BW,Tibbles LA,Muruve DA

    更新日期:2005-12-01 00:00:00

  • Neutralization profiles of primary human immunodeficiency virus type 1 isolates in the context of coreceptor usage.

    abstract::Most strains of human immunodeficiency virus type 1 (HIV-1) which have only been carried in vitro in peripheral blood mononuclear cells (primary isolates) can be neutralized by antibodies, but their sensitivity to neutralization varies considerably. To study the parameters that contribute to the differential neutraliz...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.72.9.6988-6996.1998

    authors: Cecilia D,KewalRamani VN,O'Leary J,Volsky B,Nyambi P,Burda S,Xu S,Littman DR,Zolla-Pazner S

    更新日期:1998-09-01 00:00:00

  • Interleukin-16 inhibits human immunodeficiency virus type 1 entry and replication in macrophages and in dendritic cells.

    abstract::Recombinant interleukin-16 (rIL-16) has been found to inhibit human immunodeficiency virus type 1 (HIV-1) replication in acutely or endogenously infected CD4(+) T cells. However, the effect of rIL-16 on HIV-1 replication in antigen-presenting cells (APCs) is still unknown. We show here a potent HIV-suppressive activit...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.8.7008-7013.1999

    authors: Truong MJ,Darcissac EC,Hermann E,Dewulf J,Capron A,Bahr GM

    更新日期:1999-08-01 00:00:00

  • Herpes simplex virus inhibits apoptosis through the action of two genes, Us5 and Us3.

    abstract::Apoptosis of virus-infected cells occurs either as a direct response to viral infection or upon recognition of infection by the host immune response. Apoptosis reduces production of new virus from these cells, and therefore viruses have evolved inhibitory mechanisms. We previously showed that laboratory strains of her...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.11.8950-8957.1999

    authors: Jerome KR,Fox R,Chen Z,Sears AE,Lee Hy,Corey L

    更新日期:1999-11-01 00:00:00

  • Epstein-Barr virus BZLF1 trans activator induces the promoter of a cellular cognate gene, c-fos.

    abstract::The Epstein-Barr virus BZLF1 gene product ZEBRA is a DNA-binding protein that is partially homologous to c-Fos, binds specifically to AP-1 sites, and can induce the lytic cycle in latently infected B lymphocytes. Induction of the viral lytic cycle can also be achieved by treatment with the phorbol ester 12-O-tetrade-c...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.64.9.4549-4552.1990

    authors: Flemington E,Speck SH

    更新日期:1990-09-01 00:00:00

  • Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV.

    abstract::Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.6.2740-2751.2000

    authors: Ourmanov I,Brown CR,Moss B,Carroll M,Wyatt L,Pletneva L,Goldstein S,Venzon D,Hirsch VM

    更新日期:2000-03-01 00:00:00

  • Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus.

    abstract::We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the ap...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.03462-12

    authors: Diaz-San Segundo F,Dias CC,Moraes MP,Weiss M,Perez-Martin E,Owens G,Custer M,Kamrud K,de los Santos T,Grubman MJ

    更新日期:2013-05-01 00:00:00

  • Plasma cell-specific transcription factor XBP-1s binds to and transactivates the Epstein-Barr virus BZLF1 promoter.

    abstract::Epstein-Barr virus (EBV) in vivo is known to establish persistent infection in resting, circulating memory B cells and to productively replicate in plasma cells. Until now, the molecular mechanism of how EBV switches from latency to lytic replication in vivo was not known. Here, we report that the plasma cell differen...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01055-07

    authors: Sun CC,Thorley-Lawson DA

    更新日期:2007-12-01 00:00:00

  • Dengue virus-induced modifications of host cell membranes.

    abstract::Enzymatic markers and electron microscopy were utilized to determine the cellular origin of the membrane types isolated from type 2 dengue virus-infected BHK cells by discontinuous sucrose gradient centrifugation. The results showed an apparent separation of plasma membrane, smooth and rough endoplasmic reticulum with...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.16.4.1017-1026.1975

    authors: Stohlman SA,Wisseman CL Jr,Eylar OR,Silverman DJ

    更新日期:1975-10-01 00:00:00

  • Structure of influenza virus N7: the last piece of the neuraminidase "jigsaw" puzzle.

    abstract:UNLABELLED:There are nine subtypes of influenza A virus neuraminidase (NA), N1 to N9. In addition, influenza B virus also contains NA, and there are two influenza virus NA-like molecules, N10 and N11, which were recently identified from bats. Crystal structures for all of these proteins have been solved, with the excep...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00805-14

    authors: Sun X,Li Q,Wu Y,Wang M,Liu Y,Qi J,Vavricka CJ,Gao GF

    更新日期:2014-08-01 00:00:00

  • Mutations in the matrix protein of human immunodeficiency virus type 1 inhibit surface expression and virion incorporation of viral envelope glycoproteins in CD4+ T lymphocytes.

    abstract::Highly conserved amino acids in the second helix structure of the human immunodeficiency virus type 1 (HIV-1) MA protein were identified to be critical for the incorporation of viral Env proteins into HIV-1 virions from transfected COS-7 cells. The effects of these MA mutations on viral replication in the HIV-1 natura...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.71.2.1443-1452.1997

    authors: Lee YM,Tang XB,Cimakasky LM,Hildreth JE,Yu XF

    更新日期:1997-02-01 00:00:00

  • Human APOBEC3G Prevents Emergence of Infectious Endogenous Retrovirus in Mice.

    abstract::Endogenous retroviruses (ERV) are found throughout vertebrate genomes, and failure to silence their activation can have deleterious consequences on the host. Mutation and subsequent disruption of ERV loci is therefore an indispensable component of the cell-intrinsic defenses that maintain the integrity of the host gen...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00728-19

    authors: Treger RS,Tokuyama M,Dong H,Salas-Briceno K,Ross SR,Kong Y,Iwasaki A

    更新日期:2019-09-30 00:00:00

  • Pol-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells prior to Nef-mediated major histocompatibility complex class I downregulation.

    abstract::Effective, vaccine-induced CD8+ T-cell responses should recognize infected cells early enough to prevent production of progeny virions. We have recently shown that Gag-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells at 2 h postinfection, whereas Env-specific CD8+ T cells do not recognize i...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00926-07

    authors: Sacha JB,Chung C,Reed J,Jonas AK,Bean AT,Spencer SP,Lee W,Vojnov L,Rudersdorf R,Friedrich TC,Wilson NA,Lifson JD,Watkins DI

    更新日期:2007-11-01 00:00:00

  • A patch of positively charged amino acids surrounding the human immunodeficiency virus type 1 Vif SLVx4Yx9Y motif influences its interaction with APOBEC3G.

    abstract::The amino-terminal region of the Vif molecule in human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV) contains a conserved SLV/Ix4Yx9Y motif that was first described in 1992, but the importance of this motif for Vif function has not yet been examined. Our characterization of the ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00653-09

    authors: Chen G,He Z,Wang T,Xu R,Yu XF

    更新日期:2009-09-01 00:00:00

  • Protein P4 of double-stranded RNA bacteriophage phi 6 is accessible on the nucleocapsid surface: epitope mapping and orientation of the protein.

    abstract::Protein P4, an early protein of double-stranded RNA bacteriophage phi 6, is a component of the virion-associated RNA polymerase complex and possesses a nucleoside triphosphate (NTP) phosphohydrolase activity. We have produced and characterized a panel of 20 P4-specific monoclonal antibodies. Epitope mapping using trun...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.67.5.2879-2886.1993

    authors: Ojala PM,Juuti JT,Bamford DH

    更新日期:1993-05-01 00:00:00

  • Downregulation of protein disulfide isomerase inhibits infection by the mouse polyomavirus.

    abstract::Early stages of infection by the mouse polyomavirus have been studied using HeLa cells stably expressing small interfering RNA to protein disulfide isomerase (PDI). Infectibility measured by nuclear T antigen expression was reduced commensurately with the degree of PDI downregulation. Infectibility was restored by tra...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01117-06

    authors: Gilbert J,Ou W,Silver J,Benjamin T

    更新日期:2006-11-01 00:00:00

  • Characterization of the pneumococcal bacteriophage HB-3 amidase: cloning and expression in Escherichia coli.

    abstract::HB-3, a temperate bacteriophage of Streptococcus pneumoniae, synthesizes its own murein hydrolase activity when multiplying on cultures of pneumococcus. The enzyme (HBL) was purified and biochemically characterized as an N-acetylmuramoyl-L-alanine amidase of 36,000 daltons, and a 2.1-kilobase DraI fragment containing ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.64.1.137-142.1990

    authors: Romero A,Lopez R,Garcia P

    更新日期:1990-01-01 00:00:00

  • Clink, a nanovirus-encoded protein, binds both pRB and SKP1.

    abstract::Clink, a 20-kDa protein of faba bean necrotic yellows virus, a single-stranded DNA plant virus, interacts with pRB family members and a SKP1 homologue from Medicago sativa. An LxCxE motif and an F-box of Clink mediate the interactions with the respective proteins. The capacity of Clink to bind pRB correlates with its ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.7.2967-2972.2000

    authors: Aronson MN,Meyer AD,Györgyey J,Katul L,Vetten HJ,Gronenborn B,Timchenko T

    更新日期:2000-04-01 00:00:00

  • Virion assembly defect of polyomavirus hr-t mutants: underphosphorylation of major capsid protein VP1 before viral DNA encapsidation.

    abstract::The major capsid protein of polyomavirus, VP1, was separated into at least four subspecies by isoelectric focusing. One of these subspecies was selectively extracted from purified virions by mild treatment with sodium dodecyl sulfate, leaving a 140S particle enriched in the other three forms. The two most acidic subsp...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.54.2.311-316.1985

    authors: Garcea RL,Ballmer-Hofer K,Benjamin TL

    更新日期:1985-05-01 00:00:00

  • Helper-dependent properties of Friend spleen focus-forming virus: effect of the Fv-1 gene on the late stages in virus synthesis.

    abstract::Co-infection of neonatal BALB/c mice with Friend virus (FV) complex (containing defective spleen focus-forming virus [SFFV] and endogenous N-tropic leukemia-inducing helper virus [LLV-F]) and B-tropic Tennant leukemia virus (TenLV) resulted in the inhibition of LLV-F by the Fv-1(b) gene and recovery of a TenLV pseudot...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.12.3.523-533.1973

    authors: Eckner RJ

    更新日期:1973-09-01 00:00:00

  • Role of cell-associated enveloped vaccinia virus in cell-to-cell spread.

    abstract::The roles of intracellular naked (INV), cell-associated enveloped (CEV), and extracellular enveloped (EEV) forms of vaccinia virus in cell-to-cell and longer-range spread were investigated by using two closely related strains of vaccinia virus, WR and IHD-J. We confirmed previous results that WR and IHD-J produced sim...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.66.7.4170-4179.1992

    authors: Blasco R,Moss B

    更新日期:1992-07-01 00:00:00

  • Screening of the yeast yTHC collection identifies essential host factors affecting tombusvirus RNA recombination.

    abstract::RNA recombination is a major process in promoting rapid virus evolution in an infected host. A previous genome-wide screen with the yeast single-gene deletion library of 4,848 strains, representing approximately 80% of all genes of yeast, led to the identification of 11 host genes affecting RNA recombination in Tomato...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.3.1231-1241.2006

    authors: Serviene E,Jiang Y,Cheng CP,Baker J,Nagy PD

    更新日期:2006-02-01 00:00:00