Abstract:
:Unlike RNA viruses, most DNA viruses replicate their genomes with high-fidelity polymerases that rarely make base substitution errors. Nevertheless, experimental evolution studies have revealed rapid acquisition of adaptive mutations during serial passage of attenuated vaccinia virus (VACV). One way in which adaptation can occur is by an accordion mechanism in which the gene copy number increases followed by base substitutions and, finally, contraction of the gene copy number. Here, we show rapid acquisition of multiple adaptive mutations mediated by a gene-inactivating frameshift mechanism during passage of an attenuated VACV. Attenuation had been achieved by exchanging the VACV A8R intermediate transcription factor gene with the myxoma virus ortholog. A total of seven mutations in six different genes occurred in three parallel passages of the attenuated virus. The most frequent mutations were single-nucleotide insertions or deletions within runs of five to seven As or Ts, although a deletion of 11 nucleotides also occurred, leading to frameshifts and premature stop codons. During 10 passage rounds, the attenuated VACV was replaced by the mutant viruses. At the end of the experiment, virtually all remaining viruses had one fixed mutation and one or more additional mutations. Although nucleotide substitutions in the transcription apparatus accounted for two low-frequency mutations, frameshifts in genes encoding protein components of the mature virion, namely, A26L, G6R, and A14.5L, achieved 74% to 98% fixation. The adaptive role of the mutations was confirmed by making recombinant VACV with A26L or G6R or both deleted, which increased virus replication levels and decreased particle/PFU ratios.IMPORTANCE Gene inactivation is considered to be an important driver of orthopoxvirus evolution. Whereas cowpox virus contains intact orthologs of genes present in each orthopoxvirus species, numerous genes are inactivated in all other members of the genus. Inactivation of additional genes can occur upon extensive passaging of orthopoxviruses in cell culture leading to attenuation in vivo, a strategy for making vaccines. Whether inactivation of multiple viral genes enhances replication in the host cells or has a neutral effect is unknown in most cases. Using an experimental evolution protocol involving serial passages of an attenuated vaccinia virus, rapid acquisition of inactivating frameshift mutations occurred. After only 10 passage rounds, the starting attenuated vaccinia virus was displaced by viruses with one fixed mutation and one or more additional mutations. The high frequency of multiple inactivating mutations during experimental evolution simulates their acquisition during normal evolution and extensive virus passaging to make vaccine strains.
journal_name
J Viroljournal_title
Journal of virologyauthors
Senkevich TG,Zhivkoplias EK,Weisberg AS,Moss Bdoi
10.1128/JVI.01053-20subject
Has Abstractpub_date
2020-08-31 00:00:00issue
18eissn
0022-538Xissn
1098-5514pii
JVI.01053-20journal_volume
94pub_type
杂志文章abstract::Transgene expression after the administration of recombinant adenovirus with E1 deleted is constantly transient. It is admitted that E1A-substituting activities of cellular or viral origin allow viral antigen synthesis and trigger cytotoxic lymphocyte-mediated clearance of the recipient cells. Our approach to solving ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.1.559-565.1996
更新日期:1996-01-01 00:00:00
abstract::Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1-infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing nonint...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.10.4771-4780.2006
更新日期:2006-05-01 00:00:00
abstract::Given the current difficulties generating vaccine-induced neutralizing antibodies to human immunodeficiency virus (HIV), the focus of the vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports of CTL-based vaccine trials in macaques challenged with simian/human immuno...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.24.13348-13360.2003
更新日期:2003-12-01 00:00:00
abstract::Previous analysis of hepatitis B virus (HBV) indicated base pairing between two cis-acting sequences, the 5' half of the upper stem of epsilon and phi, contributes to the synthesis of minus-strand DNA. Our goal was to identify other cis-acting sequences on the pregenomic RNA (pgRNA) involved in the synthesis of minus-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01414-07
更新日期:2007-11-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) Tat protein is essential for viral replication and stimulates transcription of the integrated provirus by recruiting the kinase complex TAK/P-TEFb, composed of cyclin T1 (CycT1) and Cdk9, to the viral TAR RNA element. TAK/P-TEFb phosphorylates the RNA polymerase II compl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.21.10579-10587.2002
更新日期:2002-11-01 00:00:00
abstract::The kinetics of retroviral DNA and RNA synthesis are parameters vital to understanding viral growth, especially for human immunodeficiency virus (HIV), which encodes several of its own regulatory genes. We have established a single-cycle growth condition for HIV in H9 cells, a human CD4+ lymphocyte line. The full-leng...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.9.3708-3713.1989
更新日期:1989-09-01 00:00:00
abstract::Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.11.5412-5419.1990
更新日期:1990-11-01 00:00:00
abstract::Murine gammaherpesvirus 68 (MHV68 [also known as gammaHV-68]) is distinguished by its ability to replicate to high titers in cultured cells, making it an excellent candidate for studying gammaherpesvirus virion composition. Extracellular MHV68 virions were isolated, and abundant virion-associated proteins were identif...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.24.13425-13432.2003
更新日期:2003-12-01 00:00:00
abstract::A substantial number of viruses have been demonstrated to subvert autophagy to promote their own replication. Recent publications have reported the proviral effect of autophagy induction on hepatitis B virus (HBV) replication. Hepatitis delta virus (HDV) is a defective virus and an occasional obligate satellite of HBV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01936-19
更新日期:2020-01-31 00:00:00
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
更新日期:2007-11-01 00:00:00
abstract::A cDNA fragment coding for poliovirus capsid polypeptide VP1 was inserted into a simian virus 40 (SV40) genome in the place of the SV40 VP1 gene and fused in phase to the 3' end of the VP2-VP3 genes. Simian cells were infected with the resulting hybrid virus in the presence of an early SV40 mutant used as a helper. In...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.12.3862-3869.1987
更新日期:1987-12-01 00:00:00
abstract::The hepatitis A virus (HAV) internal ribosome entry segment (IRES) is unique among the picornavirus IRESs in that it is inactive in the presence of either the entero- and rhinovirus 2A or aphthovirus Lb proteinases. Since these proteinases both cleave eukaryotic initiation factor 4G (eIF4G) and HAV IRES activity could...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.17.7864-7871.2001
更新日期:2001-09-01 00:00:00
abstract::Humans develop polyclonal, serotype-specific neutralizing antibody responses after dengue virus (DENV) infection. Many mouse antibodies that neutralize DENV bind to the lateral ridge or A strand epitopes on domain III of the viral envelope (EDIII) protein. It has been assumed that these epitopes are also the main targ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06871-11
更新日期:2012-04-01 00:00:00
abstract::Influenza A viruses (IAV) are lytic viruses that have recently been found to activate necroptosis in many of the cell types they infect. Necroptotic cell death is potently immunogenic and limits IAV spread by directly eliminating infected cells and by mobilizing both innate and adaptive immune responses. The benefits ...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01101-19
更新日期:2020-04-16 00:00:00
abstract::Shrimp subcuticular epithelial cells are the initial and major targets of white spot syndrome virus (WSSV) infection. Proteomic studies of WSSV-infected subcuticular epithelium of Penaeus monodon were performed through two approaches, namely, subcellular fractionation coupled with shotgun proteomics to identify viral ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01006-07
更新日期:2007-11-01 00:00:00
abstract::We established a system for propagation of Sindbis virus (SIN)-based replicons in tissue culture in the form of a tricomponent genome virus. Three RNA fragments containing complementing genetic information required for virus replication are packaged into separate viral particles, and each cell produces at least 1,000 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.1.637-643.2005
更新日期:2005-01-01 00:00:00
abstract:UNLABELLED:The extreme stability of the latent HIV-1 reservoir in the CD4(+) memory T cell population prevents viral eradication with current antiretroviral therapy. It has been demonstrated that homeostatic T cell proliferation and clonal expansion of latently infected T cells due to viral integration into specific ge...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00571-15
更新日期:2015-07-01 00:00:00
abstract::The localization of H-1 viral replicative-form double-stranded DNA and progeny single-stranded DNA replication in parasynchronously infected, simian virus 40-transformed newborn human kidney cells was studied with high-resolution electron microscope autoradiography (80-nm silver grains). We analyzed wild-type H-1 and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.1.349-360.1978
更新日期:1978-01-01 00:00:00
abstract::We recently found that a human T-cell leukemia virus type 1-infected cell line, MT-2, could support the replication of hepatitis C virus (HCV) (N. Kato, T. Nakazawa, T. Mizutani, and K. Shimotohno, Biochem. Biophys. Res. Commun. 206:863-869, 1995). In order to develop a culture system in which HCV replicates more effi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.10.7219-7223.1996
更新日期:1996-10-01 00:00:00
abstract::Our study was designed to investigate the nature of an antigen-specific suppressor factor generated by antigen-stimulated herpes simplex virus (HSV)-immune splenocytes. Factor SF-200, a 90,000- to 100,000-dalton fraction obtained after Sephacryl gel filtration, suppressed the generation of HSV-specific cytotoxic T-lym...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.2.331-338.1986
更新日期:1986-05-01 00:00:00
abstract::Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01753-20
更新日期:2021-01-13 00:00:00
abstract:UNLABELLED:The accessory gene vpr, common to all primate lentiviruses, induces potent G2/M arrest in cycling cells. A recent study showed that human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) mediates this through activation of the SLX4/MUS81/EME1 exonuclease complex that forms part of the Fanconi anem...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02307-14
更新日期:2015-01-01 00:00:00
abstract::Current L1 virus-like particle (VLP) vaccines provide type-restricted protection against a small subset of the human papillomavirus (HPV) genotypes associated with cervical cancer, necessitating continued cytologic screening of vaccinees. Cervical cancer is most problematic in countries that lack the resources for scr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01577-07
更新日期:2007-11-01 00:00:00
abstract::The structural aspects of SH antigen-containing particles were investigated. These studies confirmed the existence of a large spherical particle (ca. 43 nm) and smaller (ca. 20 nm) rod- and sphere-shaped particles. The large particle consists of an outer and inner membrane and a core of "nucleic acid" as seen by posit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.6.5.685-689.1970
更新日期:1970-11-01 00:00:00
abstract::The host cell-specific factor 1 gene (hcf-1) of the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) is required for the efficient replication and/or stability of reporter plasmids carrying an AcMNPV-derived origin of DNA replication in a cell-specific manner; hcf-1 is required for reporter plasm...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.8.5123-5130.1996
更新日期:1996-08-01 00:00:00
abstract::Members of the Flaviviridae encode a serine proteinase termed NS3 that is responsible for processing at several sites in the viral polyproteins. In this report, we show that the NS3 proteinase of the pestivirus bovine viral diarrhea virus (BVDV) (NADL strain) is required for processing at nonstructural (NS) protein si...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.7.5312-5322.1997
更新日期:1997-07-01 00:00:00
abstract::The gene encoding glycoprotein F (gF) of herpes simplex virus type 2 (HSV-2) was mapped to the region of the viral genome from 0.62 to 0.64 map units. This region is colinear with, and partially homologous to, the region of the HSV-1 genome previously shown to encode gC. Mapping of the gF gene was done by insertion of...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.3.741-747.1984
更新日期:1984-03-01 00:00:00
abstract::Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal mode...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05840-11
更新日期:2011-12-01 00:00:00
abstract::The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) of most retroviruses have a Tyr-based motif, YXXO, in their membrane-proximal regions. This signal is involved in the trafficking and endocytosis of membrane receptors via clathrin-associated AP-1 and AP-2 adaptor complexes. We have used CD8-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.2.1350-1361.1999
更新日期:1999-02-01 00:00:00
abstract::Herpes simplex virus type 2 (HSV-2) glycoprotein B (gB-2) gene segments were expressed as recombinant proteins in Escherichia coli. gB-2 recombinant proteins were reacted with human serum immunoglobulin G (IgG) antibodies in Western immunoblot assays. Initially, samples were tested for the presence of HSV-1-specific a...
journal_title:Journal of virology
pub_type: 临床试验,杂志文章
doi:10.1128/JVI.70.5.2950-2956.1996
更新日期:1996-05-01 00:00:00