Abstract:
:Parvovirus capsids are small but complex molecular machines responsible for undertaking many of the steps of cell infection, genome packing, and cell-to-cell as well as host-to-host transfer. The details of parvovirus infection of cells are still not fully understood, but the processes must involve small changes in the capsid structure that allow the endocytosed virus to escape from the endosome, pass through the cell cytoplasm, and deliver the single-stranded DNA (ssDNA) genome to the nucleus, where viral replication occurs. Here, we examine capsid substitutions that eliminate canine parvovirus (CPV) infectivity and identify how those mutations changed the capsid structure or altered interactions with the infectious pathway. Amino acid substitutions on the exterior surface of the capsid (Gly299Lys/Ala300Lys) altered the binding of the capsid to transferrin receptor type 1 (TfR), particularly during virus dissociation from the receptor, but still allowed efficient entry into both feline and canine cells without successful infection. These substitutions likely control specific capsid structural changes resulting from TfR binding required for infection. A second set of changes on the interior surface of the capsid reduced viral infectivity by >100-fold and included two cysteine residues and neighboring residues. One of these substitutions, Cys270Ser, modulates a VP2 cleavage event found in ∼10% of the capsid proteins that also was shown to alter capsid stability. A neighboring substitution, Pro272Lys, significantly reduced capsid assembly, while a Cys273Ser change appeared to alter capsid transport from the nucleus. These mutants reveal additional structural details that explain cell infection processes of parvovirus capsids. IMPORTANCE:Parvoviruses are commonly found in both vertebrate and invertebrate animals and cause widespread disease. They are also being developed as oncolytic therapeutics and as gene therapy vectors. Most functions involved in infection or transduction are mediated by the viral capsid, but the structure-function correlates of the capsids and their constituent proteins are still incompletely understood, especially in relation to identifying capsid processes responsible for infection and release from the cell. Here, we characterize the functional effects of capsid protein mutations that result in the loss of virus infectivity, giving a better understanding of the portions of the capsid that mediate essential steps in successful infection pathways and how they contribute to viral infectivity.
journal_name
J Viroljournal_title
Journal of virologyauthors
Callaway HM,Feng KH,Lee DW,Allison AB,Pinard M,McKenna R,Agbandje-McKenna M,Hafenstein S,Parrish CRdoi
10.1128/JVI.01871-16subject
Has Abstractpub_date
2017-01-03 00:00:00issue
2eissn
0022-538Xissn
1098-5514pii
JVI.01871-16journal_volume
91pub_type
杂志文章abstract::RNA packaging signals (psi) from the 5' ends of murine and avian retroviral genomes have previously been shown to direct encapsidation of heterologous mRNA into the retroviral virion. The avian 5' packaging region has now been further characterized, and we have defined a 270-nucleotide sequence, A psi, which is suffic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.1.178-188.1993
更新日期:1993-01-01 00:00:00
abstract::Utilizing a human cytomegalovirus-specific fusion inhibitor and an antiglycoprotein H antibody, we studied the role of virion fusion in interferon-stimulated gene (ISG) induction. Our results indicate that ISG induction does not occur when virion-mediated, post-high-affinity attachment events are inhibited by either r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.12.6688-6691.2004
更新日期:2004-06-01 00:00:00
abstract:UNLABELLED:Demonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus [PLRV]) an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01706-15
更新日期:2015-12-09 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor/transcription factor that modulates several cellular and immunological processes following activation by pathogen-associated stimuli, though its role during virus infection is largely unknown. Here, we show that AhR is activated in cells infected with mouse...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01743-19
更新日期:2020-01-17 00:00:00
abstract::Assembly and maturation of retroviral particles requires the aggregation and controlled proteolytic cleavage of polyprotein core precursors by a precursor-encoded protease (PR). Active, mature retroviral PR is a dimer, and the accumulation of precursors at sites of assembly may facilitate subunit interaction and subse...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.11.6165-6172.1991
更新日期:1991-11-01 00:00:00
abstract::We previously identified two novel endogenous murine leukemia virus proviruses, PreXMRV-1 and PreXMRV-2, and showed that they most likely recombined during xenograft passaging of a human prostate tumor in mice to generate xenotropic murine leukemia virus-related virus (XMRV). To determine the recombination potential o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01787-13
更新日期:2013-11-01 00:00:00
abstract::The ability of vaccinia virus to replicate in HeLa cells which had been previously infected with adenovirus type 2 (Ad2) was studied in order to gain insight into the mechanism by which adenovirus inhibits the expression of host cell functions. Vaccinia virus was employed in these studies because it replicates in the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.2.208-213.1971
更新日期:1971-02-01 00:00:00
abstract::The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into fou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00401-08
更新日期:2008-07-01 00:00:00
abstract::Reverse transcription in avian sarcoma virus (ASV) initiates from the 3' end of a tRNA(Trp) primer, which anneals near the 5' end of the RNA genome. The region around the primer-binding site (PBS) forms an elaborate stem structure composed of the U5-inverted repeat (U5-IR) stem, the U5-leader stem, and the association...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.15.7571-7577.2002
更新日期:2002-08-01 00:00:00
abstract::The complete DNA sequence of bovine adenovirus type 3 is reported here. The size of the genome is 34,446 bp in length with a G+C content of 54%. All the genes of the early and late regions are present in the expected locations of the genome. However, the late-region genes are organized into seven families, instead of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1394-1402.1998
更新日期:1998-02-01 00:00:00
abstract::The phenotypic defects of two mutants of vaccinia virus, the lesions of which map to gene G2R, were characterized in vivo, and the results suggest a role for the G2R protein in viral transcription elongation. Both a temperature-sensitive mutant, Cts56, and an isatin-beta-thiosemicarbazone-dependent deletion mutant, G2...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.1.47-54.1996
更新日期:1996-01-01 00:00:00
abstract::BALB/c mice infected on the scarified cornea with herpes simplex virus type 1 strain 35 [HSV-1(35)] rarely developed ocular disease even at challenge doses as high as 10(7) PFU per eye. In contrast, HSV-1(RE) consistently induced stromal keratitis at an inoculum of 2 x 10(4) PFU. The goal of this study was to determin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2187-2192.1990
更新日期:1990-05-01 00:00:00
abstract::A herpes simplex virus type 1 (HSV-1) strain, B3, was found to have a short duplication on the left junction between the unique sequence (US) and the inverted repeat sequence (RS) in the S component of the genome DNA. A short region of RS contiguous to the left US-RS junction was duplicated in B3. Based on the nucleot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.1877-1883.1989
更新日期:1989-05-01 00:00:00
abstract::The relative antigenicity of the individual herpes simplex virus type 1 (KOS) glycoproteins gC and gB was analyzed in BALB/c mice by using KOS mutants altered in their ability to present these antigens on cell surface membranes during infection. The mutants employed were as follows: syn LD70 , a non-temperature-sensit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.805-812.1984
更新日期:1984-06-01 00:00:00
abstract::Passage of foot-and-mouth disease virus (FMDV) in cell culture in the presence of the mutagenic base analog 5-fluorouracil or 5-azacytidine resulted in decreases of infectivity and occasional extinction of the virus. Low viral loads and low viral fitness enhanced the frequency of extinction events; this finding was sh...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.18.8316-8323.2000
更新日期:2000-09-01 00:00:00
abstract::TRIM5α is a natural resistance factor that binds retroviral capsid proteins and restricts virus replication. The B30.2/SPRY domain of TRIM5α is polymorphic in rhesus macaques, and some alleles are associated with reduced simian immunodeficiency virus (SIV) SIV(mac251) and SIV(smE543) replication in vivo. We determined...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05707-11
更新日期:2011-12-01 00:00:00
abstract::It is not yet clear to what extent depletion of intracellular GTP pools contributes to the antiviral activity of ribavirin. Therefore, the antiviral activities of (i) ribavirin, (ii) its 5-ethynyl analogue, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), and (iii) mycophenolic acid (MPA) (a compound t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.3.1943-1947.2005
更新日期:2005-02-01 00:00:00
abstract::Spatial variation in the epidemiological patterns of successive waves of pandemic influenza virus in humans has been documented throughout the 20th century but never understood at a molecular level. However, the unprecedented intensity of sampling and whole-genome sequencing of the H1N1/09 pandemic virus now makes suc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01762-10
更新日期:2011-01-01 00:00:00
abstract::LA3382 is a temperature-sensitive replication-defective mutant of Rous sarcoma virus that contains four active mutations. In this study we performed experiments to determine the biochemical defect that blocks the synthesis of infections virus late in the replication cycle. At the nonpermissive temperature (41 degrees ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.40.3.752-761.1981
更新日期:1981-12-01 00:00:00
abstract::To reliably infect a primate model for human immunodeficiency virus (HIV), approximately 10,000-fold more virus must be delivered vaginally than intravenously. However, the vaginal mechanisms that help protect against HIV are poorly understood. Here, we report that human cervicovaginal mucus (CVM), obtained from donor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01899-08
更新日期:2009-11-01 00:00:00
abstract:UNLABELLED:Hepatitis B virus (HBV) infects hundreds of millions of people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV is an enveloped virus with a relaxed circular (RC) DNA genome. In the nuclei of infected human hepatocytes, conversion of RC DNA from the incoming viri...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01263-15
更新日期:2015-10-21 00:00:00
abstract::Respiratory syncytial virus (RSV) infection of children previously immunized with a nonlive, formalin-inactivated (FI)-RSV vaccine has been associated with serious enhanced respiratory disease (ERD). Consequently, detailed studies of potential ERD are a critical step in the development of nonlive RSV vaccines targetin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02180-16
更新日期:2017-03-29 00:00:00
abstract::The entire genome of the reference strain of bluetongue virus (BTV) serotype 16 (strain RSArrrr/16) was sequenced (a total of 23,518 base pairs). The virus was obtained from the Orbivirus Reference Collection (ORC) at IAH, Pirbright, United Kingdom. The virus strain, which was previously provided by the Onderstepoort ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01672-12
更新日期:2012-09-01 00:00:00
abstract::During lytic infection, the genome of herpes simplex virus 1 (HSV-1) is associated with limited levels of histones but does not form a regular repeating nucleosomal structure. However, the previous observation that chromatin remodeling factors are recruited into viral replication compartments indicates that chromatin ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01575-08
更新日期:2008-12-01 00:00:00
abstract::p60src, the transforming protein of Rous sarcoma virus, was found to contain 0.5 to 0.9 mol of total phosphate per mol of polypeptide. The protein is known to be phosphorylated at two sites, a serine in the amino-terminal domain and a tyrosine in the carboxy-terminal domain. Because our indirect analysis suggests that...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.41.3.813-820.1982
更新日期:1982-03-01 00:00:00
abstract::Andes virus (ANDV) causes a fatal hantavirus pulmonary syndrome (HPS) in humans and Syrian hamsters. Human alpha(v)beta(3) integrins are receptors for several pathogenic hantaviruses, and the function of alpha(v)beta(3) integrins on endothelial cells suggests a role for alpha(v)beta(3) in hantavirus directed vascular ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01013-09
更新日期:2010-01-01 00:00:00
abstract::Mus dunni endogenous virus (MDEV) is activated from cells of the Asian wild mouse M. dunni (also known as Mus terricolor) in response to treatment with either 5-iodo-2'-deoxyuridine or hydrocortisone. MDEV represents a new murine retrovirus interference group and thus appears to use a different receptor for entry into...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.6.4663-4670.1997
更新日期:1997-06-01 00:00:00
abstract::Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02324-16
更新日期:2017-03-13 00:00:00
abstract::The gene encoding glycoprotein B (gB) of murine cytomegalovirus (MCMV) strain Smith was identified, sequenced, and expressed by recombinant vaccinia virus. The gB gene was found adjacent to the polymerase gene, as it is in the genome of human cytomegalovirus (HCMV). The open reading frame consists of 2,784 nucleotides...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4399-4406.1992
更新日期:1992-07-01 00:00:00
abstract::Hepadnaviruses contain a relaxed circular DNA genome (RC-DNA) with discontinuities in both strands. Upon infectious entry into a host cell, this genome is converted into a covalently closed superhelical form (CCC-DNA), which later serves as the template for transcription. Here we examined whether the viral polymerase ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4867-4874.1993
更新日期:1993-08-01 00:00:00