Abstract:
:Hepatitis C virus (HCV) infection remains a major worldwide health problem despite development of highly effective direct-acting antivirals. HCV rapidly evolves upon acute infection and generates multiple viral variants (quasispecies), leading to immune evasion and persistent viral infection. Identification of epitopes of broadly neutralizing anti-HCV antibodies (nAbs) is critical to guide HCV vaccine development. In this study, we developed a new reverse genetics system for HCV infection based on trans-complementation of viral structural proteins. The HCV genome (JFH1 strain) lacking the structural protein-coding sequence can be efficiently rescued by ectopic expression of core-E1-E2-p7-NS2 (core-NS2) or core-E1-E2-p7 (core-p7) in trans, leading to production of single-round infectious virions designated HCVΔS. JFH1-based HCVΔS can be also rescued by expressing core-NS2 of other HCV genotypes, rendering it an efficient tool to display the structural proteins of HCV strains of interests. Furthermore, we successfully rescued HCVΔS with structural proteins from clinical isolates. Multiple viral structural proteins with different sensitivities to nAbs were identified from a same patient serum, demonstrating the genetic diversity of HCV quasispecies in vivo Interestingly, the structural protein-coding sequences of highly divergent viral quasispecies from the same patient can be clustered based on their hypervariable region 1 (HVR1) in viral envelope protein E2, which critically dictates the sensitivity to neutralizing antibodies. In summary, we developed a novel reverse genetics system that efficiently displays viral structural proteins from HCV clinical isolates, and analysis of quasispecies from the same patient using this system demonstrated that E2 HVR1 is the major determinant of viral evolution in vivoIMPORTANCE A cell culture model that can recapitulate the diversity of HCV quasispecies in patients is important for analysis of neutralizing epitopes and HCV vaccine development. In this study, we developed a new reverse genetics system for HCV infection based on trans-complementation of viral structural proteins (HCVΔS). This system can be used to display structural proteins of HCV strains of multiple genotypes as well as clinical isolates. By using this system, we showed that multiple different HCV structural proteins from a same patient were displayed on HCVΔS. Interestingly, these variant structural proteins within the same patient can be classified according to the sequence of HVR1in E2, which dictates viral sensitivity to nAbs and viral evolution in vivo Our work provided a new tool to study highly divergent HCV quasispecies and shed light on underlying mechanisms driving HCV evolution.
journal_name
J Viroljournal_title
Journal of virologyauthors
Tong Y,Li Q,Li R,Xu Y,Pan Y,Niu J,Zhong Jdoi
10.1128/JVI.00622-20subject
Has Abstractpub_date
2020-08-17 00:00:00issue
17eissn
0022-538Xissn
1098-5514pii
JVI.00622-20journal_volume
94pub_type
杂志文章abstract::Since its detection in swine, influenza D virus (IDV) has been shown to be present in multiple animal hosts, and bovines have been identified as its natural reservoir. However, it remains unclear how IDVs emerge, evolve, spread, and maintain in bovine populations. Through multiple years of virological and serological ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00240-20
更新日期:2020-08-31 00:00:00
abstract::Two poliovirus mutants were isolated that contain an oligonucleotide linker insertion in the 2C-coding region of the viral genome. One, 2C-31, has a strongly temperature-sensitive phenotype and the other, 2C-32, forms small plaques on HeLa cell monolayers at all temperatures. Both mutants have a severe temperature-sen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.11.4016-4021.1988
更新日期:1988-11-01 00:00:00
abstract::Here, we report that specific manipulations of the cellular response to virus infection can cause prevention of apoptosis and consequent establishment of persistent infection. Infection of several human cell lines with Sendai virus (SeV) or human parainfluenza virus 3, two prototypic paramyxoviruses, caused slow apopt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02536-07
更新日期:2008-04-01 00:00:00
abstract::A number of positive-strand RNA viruses, such as hepatitis C virus (HCV) and poliovirus, use double-membrane vesicles (DMVs) as replication sites. However, the role of cellular proteins in DMV formation during virus replication is poorly understood. HCV NS4B protein induces the formation of a "membranous web" structur...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00858-19
更新日期:2020-01-06 00:00:00
abstract::The sequence relations between Kirsten murine sarcoma virus (Ki-SV), Harvey murine sarcoma virus (Ha-SV), and a rat endogenous 30S RNA were studied by electron microscope heteroduplex analysis. The sequence relationships between the sarcoma viruses and their respective parental murine leukemia viruses (Kirsten and Mol...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.31.3.752-760.1979
更新日期:1979-09-01 00:00:00
abstract::Under the immune pressure of cytotoxic T cells (CTLs), hepatitis B virus (HBV) evolves to accumulate mutations more likely within epitopes to evade immune detection. However, little is known about the specific patterns of the immune pressure-associated HBV mutation of T-cell epitopes and their link to disease progress...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02120-17
更新日期:2018-08-16 00:00:00
abstract::Human immunodeficiency virus type 1 infection of mononuclear phagocytes has been implicated in disease manifestations, but postentry viral replication events in these cells have not been well characterized. Productive infection of activated T cells is associated with cell proliferation and accumulation of full-length ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.2.1258-1263.1994
更新日期:1994-02-01 00:00:00
abstract::Klebsiella pneumoniae is a member of the family Enterobacteriaceae, opportunistic pathogens that are among the eight most prevalent infectious agents in hospitals. The emergence of multidrug-resistant strains of K. pneumoniae has became a public health problem globally. To develop an effective antimicrobial agent, we ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02435-12
更新日期:2012-12-01 00:00:00
abstract::The nucleic acids of influenza A, B, and C viruses were compared. Susceptibility to nucleases demonstrates that influenza C virus, just as influenza A and B viruses, possesses single-stranded RNA as its genome. The base compositions of the RNAs of influenza A, B, and influenza C virus are almost identical and comparat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.2.738-744.1976
更新日期:1976-05-01 00:00:00
abstract::Titers of vaccinia virus consistently increased in cultures of washed phytohemagglutinin-treated, peripheral blood leukocytes of a vaccinated adult. Concomitantly, a gradual rise occurred in the numbers of infected leukocytes, as determined by the infective center assay. Increase in viral titer was accompanied by cell...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.8.787-792.1968
更新日期:1968-08-01 00:00:00
abstract::Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01525-12
更新日期:2012-11-01 00:00:00
abstract::Adenoviral RNA sequences synthesized in nuclei isolated during the late phase of productive infection comprise, besides virus-associated, VA, RNA, five major species, ranging in size from approximately 13S to 55S. The latter RNA species is of the length predicted if the major transcriptional unit expressed during the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.32.2.394-403.1979
更新日期:1979-11-01 00:00:00
abstract::In 2010 and 2011, several devastating Newcastle disease (ND) outbreaks occurred in China, affecting broilers, layers, and breeders. The CK-JSX1-201005 virus was isolated from broiler breeder flocks vaccinated with the classical ND virus (NDV) vaccine program, but laying rate decreased from 80% to 30 to 40% in the clin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02314-12
更新日期:2012-11-01 00:00:00
abstract::The synthesis of closed circular simian virus 40 (SV40) deoxyribonucleic acid (DNA) containing sequences homologous to host cell DNA depends upon the conditions under which the cells are infected. When BS-C-1 monkey cells were infected with non-plaque-purified virus at low multiplicity of infection [MOI, 0.032 plaque-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.2.309-316.1972
更新日期:1972-02-01 00:00:00
abstract::The chimeric murine oncornavirus FrCas(E) causes a rapidly progressive paralytic disease associated with spongiform neurodegeneration throughout the neuroaxis. Neurovirulence is determined by the sequence of the viral envelope gene and by the capacity of the virus to infect microglia. The neurocytopathic effect of thi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.6.2665-2674.2001
更新日期:2001-03-01 00:00:00
abstract::To analyze intrauterine transmission, MT-2 cells, a human T-cell line producing human T-cell leukemia virus type I (HTLV-I), were injected into eight pregnant F344 rats, and cesarean section was performed at day 23 of pregnancy. HTLV-I provirus was detected by PCR in the liver and spleen taken from one of the eight fe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.2.1302-1305.1995
更新日期:1995-02-01 00:00:00
abstract:UNLABELLED:Viral myocarditis, which is most prevalently caused by coxsackievirus B3 (CVB3), is a serious clinical condition characterized by excessive myocardial inflammation. Recent studies suggest that regulation of protein acetylation levels by inhibiting histone deacetylase (HDAC) activity modulates inflammatory re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01028-15
更新日期:2015-10-01 00:00:00
abstract::Wild-type simian virus 40 A protein (large T antigen) bound to three tandem regions of simian virus 40 DNA. The binding regions were defined by the ability of A protein to protect simian virus 40 DNA from digestion with limited (footprint assay) or excess (fragment assay) amounts of DNase I. At low concentrations, pro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.2.458-466.1982
更新日期:1982-11-01 00:00:00
abstract::The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02472-07
更新日期:2008-05-01 00:00:00
abstract::Human enterovirus 71 (EV-71) is one of the major etiologic causes of hand, foot, and mouth disease (HFMD) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. Global VP1 capsid sequences (n = 628) sampled over 4 decades were collected and subjected to compreh...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01019-09
更新日期:2010-04-01 00:00:00
abstract::We have designed a ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in U5 (at nucleotide +115). This ribozyme was tested in vitro and was found to give efficient and specific digestion of RNA containing the HIV-1 U5 sequence. When the U5 ribozyme was placed into the HIV-1 genome, virus replication...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.3.1432-1441.1992
更新日期:1992-03-01 00:00:00
abstract::The genome of murine cytomegalovirus, extracted from extracellular virions, is a linear double-stranded DNA molecule ca. 240 kilobase pairs long. In our initial cloning of subgenomic fragments of the murine cytomegalovirus genome, we obtained a HindIII clone which contained fused HindIII-terminal fragments. By hybridi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.1.24-28.1984
更新日期:1984-10-01 00:00:00
abstract::During herpes simplex virus (HSV) latency, most viral genes are silenced, with the exception of one region of the genome encoding the latency-associated transcript (LAT). This long noncoding RNA was originally described as having a role in enhancing HSV-1 reactivation. However, subsequent evidence showing that the LAT...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00812-18
更新日期:2018-07-31 00:00:00
abstract::The transforming proteins of the small DNA tumor viruses, simian virus 40 (SV40), adenovirus, and human papillomavirus (HPV) target a number of identical cellular regulators whose functional abrogation is required for transformation. However, while both adenovirus E1A and SV40 large T transforming properties also depe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.6209-6219.1999
更新日期:1999-08-01 00:00:00
abstract::Humans chronically infected with hepatitis B virus (HBV) are at further risk of liver cancer upon exposure to dietary aflatoxin B1 (AFB1), a carcinogenic product of the mold Aspergillus flavus. For the present study, we utilized double-transgenic mice (ATX mice) that express the HBV X protein (HBx) and possess a bacte...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.22.11770-11774.2002
更新日期:2002-11-01 00:00:00
abstract::We have isolated a new type of temperature-sensitive mutant of simian virus 40 (SV40) that is capable of productive infection in permissive cells but not of maintenance of viral DNA integration in transformed cells at the conditional temperature. Virus development is induced when cells transformed by this mutant are s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.19.2.374-381.1976
更新日期:1976-08-01 00:00:00
abstract::Replicase gene expression by the human coronavirus 229E involves the synthesis of two large polyproteins, pp1a and pp1ab. Experimental evidence suggests that these precursor molecules are subject to extensive proteolytic processing. In this study, we show that a chymotrypsin-like enzyme, the virus-encoded 3C-like prot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.1.177-185.1999
更新日期:1999-01-01 00:00:00
abstract::In coliphage 186, 22 essential genes were defined by complementation studies with amber mutants. Eighteen genes were associated with phage morphogenesis: 11 with phage tail formation, and 7 with phage head formation. The remaining four genes are discussed in the accompanying paper (S. M. Hocking and J. B. Egan, J. Vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.3.1056-1067.1982
更新日期:1982-12-01 00:00:00
abstract::The product of the v-myb oncogene of avian myeloblastosis virus is a nuclear protein with an associated DNA-binding activity. We demonstrated that the highly conserved amino-terminal domain of p48v-myb is required for its associated DNA-binding activity. This activity is not required for the nuclear localization of p4...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.11.4398-4402.1988
更新日期:1988-11-01 00:00:00
abstract::The herpes simplex virus type 1 (HSV-1) ICP34.5 gene is a neurovirulence gene in mice. In addition, some ICP34.5 mutants have been reported to have a reduced efficiency of induced reactivation as measured by in vitro explantation of latently infected mouse ganglia. However, since spontaneous reactivation is almost non...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.5.3033-3041.1995
更新日期:1995-05-01 00:00:00