Abstract:
UNLABELLED:JC polyomavirus (JCPyV) infection of immunocompromised individuals results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). The viral capsid of JCPyV is composed primarily of the major capsid protein virus protein 1 (VP1), and pentameric arrangement of VP1 monomers results in the formation of a pore at the 5-fold axis of symmetry. While the presence of this pore is conserved among polyomaviruses, its functional role in infection or assembly is unknown. Here, we investigate the role of the 5-fold pore in assembly and infection of JCPyV by generating a panel of mutant viruses containing amino acid substitutions of the residues lining this pore. Multicycle growth assays demonstrated that the fitness of all mutants was reduced compared to that of the wild-type virus. Bacterial expression of VP1 pentamers containing substitutions to residues lining the 5-fold pore did not affect pentamer assembly or prevent association with the VP2 minor capsid protein. The X-ray crystal structures of selected pore mutants contained subtle changes to the 5-fold pore, and no other changes to VP1 were observed. Pore mutant pseudoviruses were not deficient in assembly, packaging of the minor capsid proteins, or binding to cells or in transport to the host cell endoplasmic reticulum. Instead, these mutant viruses were unable to expose VP2 upon arrival to the endoplasmic reticulum, a step that is critical for infection. This study demonstrated that the 5-fold pore is an important structural feature of JCPyV and that minor modifications to this structure have significant impacts on infectious entry. IMPORTANCE:JCPyV is an important human pathogen that causes a severe neurological disease in immunocompromised individuals. While the high-resolution X-ray structure of the major capsid protein of JCPyV has been solved, the importance of a major structural feature of the capsid, the 5-fold pore, remains poorly understood. This pore is conserved across polyomaviruses and suggests either that these viruses have limited structural plasticity in this region or that this pore is important in infection or assembly. Using a structure-guided mutational approach, we showed that modulation of this pore severely inhibits JCPyV infection. These mutants do not appear deficient in assembly or early steps in infectious entry and are instead reduced in their ability to expose a minor capsid protein in the host cell endoplasmic reticulum. Our work demonstrates that the 5-fold pore is an important structural feature for JCPyV.
journal_name
J Viroljournal_title
Journal of virologyauthors
Nelson CD,Ströh LJ,Gee GV,O'Hara BA,Stehle T,Atwood WJdoi
10.1128/JVI.00089-15subject
Has Abstractpub_date
2015-04-01 00:00:00pages
3910-21issue
7eissn
0022-538Xissn
1098-5514pii
JVI.00089-15journal_volume
89pub_type
杂志文章abstract::The mechanism by which simian virus 40 converts the abortive adenovirus type 7 infection of monkey cells into an efficient lytic infection has been investigated. Analysis of ribonucleic acid (RNA) synthesis during unenhanced and enhanced infection of monkey cells has shown that adenovirus RNA synthesized in the aborti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.2.220-227.1972
更新日期:1972-08-01 00:00:00
abstract::The 5' untranslated region (UTR) of hepatitis C virus (HCV), which is composed of four domains (I, II, III, and IV) and a pseudoknot, is essential for translation and viral replication. Equine nonprimate hepacivirus (EHcV) harbors a 5' UTR consisting of a large 5'-terminal domain (I); three additional domains (I', II,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01997-17
更新日期:2018-03-14 00:00:00
abstract::Amino acid analysis of [3H]proline-labeled polyomavirus major capsid protein VP1 by two-dimensional paper chromatography of the acid-hydrolyzed protein revealed the presence of 3H-labeled hydroxyproline. Addition of the proline analog L-azetidine-2-carboxylic acid to infected mouse kidney cell cultures prevented or gr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.6.2881-2884.1989
更新日期:1989-06-01 00:00:00
abstract::By using temperature-sensitive (ts) and suppressor-sensitive (sus) mutants, 11 essential genes have been identified in phage phi105. The order of the genes has been established in two- and three-factor crosses. The genes can be arranged in a linear order; this order is identical in the vegetative phage and in the prop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.6.6.760-767.1970
更新日期:1970-12-01 00:00:00
abstract::During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05873-11
更新日期:2011-12-01 00:00:00
abstract::Latent HIV proviruses are silenced as the result of deacetylation and methylation of histones located at the viral long terminal repeat (LTR). Inhibition of histone deacetylases (HDACs) leads to the reemergence of HIV-1 from latency, but the contribution of histone lysine methyltransferases (HKMTs) to maintaining HIV ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00836-11
更新日期:2011-09-01 00:00:00
abstract::Two chimpanzees immunized with woodchuck hepatitis virus (WHV) surface antigen (WHsAg) developed antibodies cross-reactive with hepatitis B virus (HBV) surface antigen (HBsAg). After challenge with HBV, one animal was completely protected and the other experienced a subclinical infection, without evidence of liver dis...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.3.895-901.1986
更新日期:1986-12-01 00:00:00
abstract::A recent experiment involving simian immunodeficiency virus (SIV) infection of macaques revealed that the infectivity of this virus decreased over the first few months of infection. Based on this observation, we introduce a viral dynamic model in which viral infectivity varies over time. The model is fit to viral load...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02284-09
更新日期:2010-05-01 00:00:00
abstract::Long-acting antiretrovirals could provide a useful alternative to daily oral therapy for HIV-1-infected individuals. Building on a bi-specific molecule with adnectins targeting CD4 and gp41, a potential long-acting biologic, GSK3732394, was developed with three independent and synergistic modes of HIV entry inhibition...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00907-19
更新日期:2019-09-30 00:00:00
abstract::High-risk human papillomavirus type 16 (HPV16) is the primary causative agent of cervical cancer and therefore is responsible for significant morbidity and mortality worldwide. Cellular transformation is mediated directly by the expression of viral oncogenes, the least characterized of which, E5, subverts cellular pro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06243-11
更新日期:2012-05-01 00:00:00
abstract::A closed circular, double-stranded infectious DNA of Moloney leukemia virus has been described previously. The present report characterizes a second type of infectious, unintegrated viral DNA which is linear, largely double stranded, and of mass comparable to that of the closed circular viral DNA. The linear form is o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.20.3.621-626.1976
更新日期:1976-12-01 00:00:00
abstract::Poliovirus infection of HeLa cells results in a rapid inhibition of host protein synthesis by a mechanism that does not affect the translation of poliovirus RNA. It has been suggested that this virus-induced translational control results from inactivation of the cap-binding protein complex, and it has been shown that ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.8.2480-2488.1987
更新日期:1987-08-01 00:00:00
abstract::Lysine-specific demethylase 1 (LSD1) targets cellular proteins, including histone H3, p53, E2F, and Dnmt1, and is involved in the regulation of gene expression, DNA replication, the cell cycle, and the DNA damage response. LSD1 catalyzes demethylation of histone H3K9 associated with herpes simplex virus 1 (HSV-1) imme...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00974-20
更新日期:2020-09-15 00:00:00
abstract::Radioimmunoassays were developed for the 19,000, 15,000, and 12,000 molecular weight polypeptides of avian myeloblastosis virus and for the 19,000 and 12,000 polypeptides of RAV-0, a subgroup E avian tumor virus. Each polypeptide was shown to possess both group- and type-specific antigenic determinants, in contrast to...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.1.27-33.1975
更新日期:1975-07-01 00:00:00
abstract::We previously described that type B retrovirus-like particles released from the human mammary carcinoma cell line T47D are pseudotypes and package retroviral RNA of different origins (W. Seifarth, H. Skladny, F. Krieg-Schneider, A. Reichert, R. Hehlmann, and C. Leib-Mösch, J. Virol. 69:6408-6416, 1995). One preferenti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.8384-8391.1998
更新日期:1998-10-01 00:00:00
abstract::The open reading frame III of Borna disease virus (BDV) codes for a protein with a mass of 16 kDa, named p16 or BDV-M. p16 was described as an N-glycosylated protein in several previous publications and therefore was termed gp18, although the amino acid sequence of p16 does not contain any regular consensus sequence f...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.24.12098-12104.2001
更新日期:2001-12-01 00:00:00
abstract::AIDS vaccination has a pressing need for more potent vaccination vectors capable of eliciting strong, diversified, and long-lasting cellular immune responses against human immunodeficiency virus (HIV). Lentiviral vectors have demonstrated efficiency not only as gene delivery vehicles for gene therapy applications but ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01284-09
更新日期:2009-11-01 00:00:00
abstract::Infection and transformation of chondrocytes by Rous sarcoma viruses (RSVs) (Schmidt-Ruppin, Prague) stimulated the rate of cell growth. In contrast, several transformation-defective (td) mutants (tdPRA, tdNY105, tdNY106, tdNY107, and tdNY108) retaining various sizes of the src gene did not stimulate cell growth, indi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.2.531-541.1980
更新日期:1980-08-01 00:00:00
abstract::Antibody was raised against purified vaccinia virus RNA polymerase and used to screen a recombinant vaccinia virus-lambda gt11 library. The DNA from several immunopositive clones was shown by Southern hybridization to originate from the vaccinia virus HindIII E fragment. The nucleotide sequence of the RNA polymerase s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.11.5376-5382.1990
更新日期:1990-11-01 00:00:00
abstract::TMC114, a newly designed human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is extremely potent against both wild-type (wt) and multidrug-resistant (MDR) viruses in vitro as well as in vivo. Although chemically similar to amprenavir (APV), the potency of TMC114 is substantially greater. To examine the bas...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.21.12012-12021.2004
更新日期:2004-11-01 00:00:00
abstract::The TAATGARAT motif in the herpes simplex virus (HSV) immediate-early (IE) gene promoters plays a key role in their activation by the Oct-1-Vmw65 complex, but its role in mediating inhibitory effects of cellular octamer-binding proteins is less clear. We have used indicator viruses containing reporter constructs with ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.4.3495-3500.1998
更新日期:1998-04-01 00:00:00
abstract::The Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) protein is a transcriptional regulator of viral and cellular genes that is essential for EBV-mediated immortalization of B lymphocytes in vitro. EBNA-3C can inhibit transcription through an association with the cellular DNA-binding protein Jkappa, a function sh...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.11.5151-5160.2000
更新日期:2000-06-01 00:00:00
abstract::The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses carries out three discrete activities that each affect the ability of HN to promote viral fusion and entry: receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein. The interrelationship between the receptor binding and f...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02617-06
更新日期:2007-04-01 00:00:00
abstract::Inoculation of 3-day-old (3D) or 3-week-old (3W) ducklings with duck hepatitis B virus results in chronic or transient infection, respectively. We previously showed that rapid production of neutralizing antibody following inoculation of 3W ducklings prevents virus from spreading in the liver and leads to a transient i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.15.9896-9903.2005
更新日期:2005-08-01 00:00:00
abstract::The VP6 protein of bluetongue virus possesses a number of activities, including nucleoside triphosphatase, RNA binding, and helicase activity (N. Stauber, J. Martinez-Costas, G. Sutton, K. Monastyrskaya, and P. Roy, J. Virol. 71:7220-7226, 1997). Although the enzymatic functions of the protein have been documented, a ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.21.11347-11356.2003
更新日期:2003-11-01 00:00:00
abstract:UNLABELLED:Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. Since its discovery in the 1970s, aMPV has been recognized as an economically important pathogen in the pou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01095-14
更新日期:2014-11-01 00:00:00
abstract::Incorporation of the vaccinia virus A36R protein into the outer membrane of intracellular enveloped virions (IEV) is dependent on expression of the A33R protein. Possible interactions of the 200-amino-acid cytoplasmic domain of the A36R protein with itself or with the cytoplasmic domain of the A33R, A34R, B5R, or F12L...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.7.4113-4126.2003
更新日期:2003-04-01 00:00:00
abstract::WUH4 is a highly pathogenic North American porcine reproductive and respiratory syndrome virus (PRRSV). Unlike previous PRRSV isolates, which were mainly recovered from sera or tissues, WUH4 was isolated from a piglet stool sample. Here we announce its complete genome sequence. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00055-12
更新日期:2012-04-01 00:00:00
abstract::Primary RNA transcripts from the human immunodeficiency virus type 1 (HIV-1) are processed into mature mRNA by a complex series of splicing events. Viral structural proteins and reverse transcriptase are translated from unspliced or singly spliced transcripts. Proteins which control virus replication, including tat, r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.7.3391-3398.1990
更新日期:1990-07-01 00:00:00
abstract:UNLABELLED:Children with acute respiratory syncytial virus (RSV) infection often develop sequelae of persistent airway inflammation and wheezing. Pulmonary C fibers (PCFs) are involved in the generation of airway inflammation and resistance; however, their role in persistent airway diseases after RSV is unexplored. Her...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02534-15
更新日期:2015-12-16 00:00:00