Abstract:
:The hemagglutinin (HA), a glycoprotein on the surface of influenza A virus (IAV), initiates the virus life cycle by binding to terminal sialic acid (SA) residues on host cells. The HA gradually accumulates amino acid substitutions that allow IAV to escape immunity through a mechanism known as antigenic drift. We recently confirmed that a small set of amino acid residues are largely responsible for driving antigenic drift in swine-origin H3 IAV. All identified residues are located adjacent to the HA receptor binding site (RBS), suggesting that substitutions associated with antigenic drift may also influence receptor binding. Among those substitutions, residue 145 was shown to be a major determinant of antigenic evolution. To determine whether there are functional constraints to substitutions near the RBS and their impact on receptor binding and antigenic properties, we carried out site-directed mutagenesis experiments at the single-amino-acid level. We generated a panel of viruses carrying substitutions at residue 145 representing all 20 amino acids. Despite limited amino acid usage in nature, most substitutions at residue 145 were well tolerated without having a major impact on virus replication in vitro All substitution mutants retained receptor binding specificity, but the substitutions frequently led to decreased receptor binding. Glycan microarray analysis showed that substitutions at residue 145 modulate binding to a broad range of glycans. Furthermore, antigenic characterization identified specific substitutions at residue 145 that altered antibody recognition. This work provides a better understanding of the functional effects of amino acid substitutions near the RBS and the interplay between receptor binding and antigenic drift.IMPORTANCE The complex and continuous antigenic evolution of IAVs remains a major hurdle for vaccine selection and effective vaccination. On the hemagglutinin (HA) of the H3N2 IAVs, the amino acid substitution N 145 K causes significant antigenic changes. We show that amino acid 145 displays remarkable amino acid plasticity in vitro, tolerating multiple amino acid substitutions, many of which have not yet been observed in nature. Mutant viruses carrying substitutions at residue 145 showed no major impairment in virus replication in the presence of lower receptor binding avidity. However, their antigenic characterization confirmed the impact of the 145 K substitution in antibody immunodominance. We provide a better understanding of the functional effects of amino acid substitutions implicated in antigenic drift and its consequences for receptor binding and antigenicity. The mutation analyses presented in this report represent a significant data set to aid and test the ability of computational approaches to predict binding of glycans and in antigenic cartography analyses.
journal_name
J Viroljournal_title
Journal of virologyauthors
Santos JJS,Abente EJ,Obadan AO,Thompson AJ,Ferreri L,Geiger G,Gonzalez-Reiche AS,Lewis NS,Burke DF,Rajão DS,Paulson JC,Vincent AL,Perez DRdoi
10.1128/JVI.01413-18subject
Has Abstractpub_date
2019-01-04 00:00:00issue
2eissn
0022-538Xissn
1098-5514pii
JVI.01413-18journal_volume
93pub_type
杂志文章abstract::Visna lentiviruses have a natural tropism for cells of the macrophage lineage of sheep and goats, but virus replication in these cells in vivo is restricted so that only small quantities of virus are produced. One restricting factor suggested in previous studies is that virus replication is dependent on the maturity o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.1.67-74.1986
更新日期:1986-04-01 00:00:00
abstract::We have previously identified a functionally essential bulged stem-loop in the 3' untranslated region of the positive-stranded RNA genome of mouse hepatitis virus. This 68-nucleotide structure is composed of six stem segments interrupted by five bulges, and its structure, but not its primary sequence, is entirely cons...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.15.6911-6921.2000
更新日期:2000-08-01 00:00:00
abstract::Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human mi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00026-18
更新日期:2018-03-14 00:00:00
abstract::It has been previously shown that rotavirus maturation and stability of the outer capsid are calcium-dependent processes. More recently, it has been hypothesized that penetration of the cell membrane is also affected by conformational changes of the capsid induced by Ca2+. In this study, we determined quantitatively t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.8.4877-4883.1996
更新日期:1996-08-01 00:00:00
abstract::Viral attenuation may be due to lowered efficiency of certain steps essential for viral multiplication. For the construction of less neurovirulent strains of poliovirus in vitro, we introduced deletions into the 5' noncoding sequence (742 nucleotides long) of the genomes of the Mahoney and Sabin 1 strains of polioviru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.12.5354-5363.1989
更新日期:1989-12-01 00:00:00
abstract::Adeno-associated virus type 2 (AAV-2) gene expression is tightly controlled by functions of the helper virus as well as by the products of its own viral rep gene. Double-immunofluorescence studies of Rep and VP protein expression in cells coinfected with AAV-2 and adenovirus type 2 showed that a large proportion of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8437-8447.1997
更新日期:1997-11-01 00:00:00
abstract::Human herpesvirus 6 (HHV-6) has a tropism for T lymphocytes and monocytes/macrophages, suggesting that HHV-6 infection affects the immunosurveillance system. In the present study, we investigated the HHV-6-induced phenotypic and functional alterations of dendritic cells (DCs), which are professional antigen-presenting...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.20.10338-10345.2002
更新日期:2002-10-01 00:00:00
abstract::Activation of the interferon-inducible, double-stranded RNA-dependent protein kinase was monitored in monolayer cultures of control and interferon-treated HeLa cells infected with encephalomyocarditis virus. The extent of phosphorylation in the intact cell of the alpha-subunit of eucaryotic protein synthesis initiatio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.3.894-898.1985
更新日期:1985-06-01 00:00:00
abstract:UNLABELLED:In a genome-wide small interfering RNA (siRNA) screen, we recently identified the interferon (IFN)-inducible protein 35 (IFI35; also known as IFP35) as a factor required for vesicular stomatitis virus (VSV) infection. Studies reported here were conducted to further understand the role and requirement of IFI3...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03202-13
更新日期:2014-03-01 00:00:00
abstract::The minor glycoproteins from hepatitis B surface antigen, GP33 and GP36, contain at their carboxy-terminal part the sequence of the major protein P24. They have 55 additional amino acids at the amino-terminal part which are coded by the pre-S region of the viral DNA. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.2.626-628.1983
更新日期:1983-05-01 00:00:00
abstract::Interactions between host factors and the viral replication complex play important roles in host adaptation and regulation of influenza virus replication. A cellular protein, nuclear factor 90 (NF90), was copurified with H5N1 viral nucleoprotein (NP) from human cells in which NP was transiently expressed and identifie...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00735-09
更新日期:2009-08-01 00:00:00
abstract::In all retroviruses analyzed to date (except for the spumaretroviruses), the Zn(2+)-coordinating residues of nucleocapsid (NC) perform or assist in crucial reactions necessary to complete the retrovirus life cycle. Six replication-defective mutations have been engineered in the two NC Zn(2+) fingers (ZFs) of simian im...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.1.115-124.2001
更新日期:2001-01-01 00:00:00
abstract::While a diversity of immunogens that elicit qualitatively different cellular immune responses are being assessed in clinical human immunodeficiency virus vaccine trials, the consequences of those varied responses for viral control remain poorly understood. In the present study, we evaluated the induction of virus-spec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00204-08
更新日期:2008-09-01 00:00:00
abstract::A significant percentage of the population latently harbors Epstein-Barr virus (EBV) in B cells. One EBV-encoded protein, latent membrane protein 2A (LMP2A), is expressed in tissue culture models of EBV latent infection, in human infections, and in many of the EBV-associated proliferative disorders. LMP2A constitutive...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.12.7355-7362.2005
更新日期:2005-06-01 00:00:00
abstract::Infectious bursal disease virus (IBDV), a double-stranded RNA (dsRNA) virus belonging to the Birnaviridae family, is an economically important avian pathogen. The IBDV capsid is based on a single-shelled T=13 lattice, and the only structural subunits are VP2 trimers. During capsid assembly, VP2 is synthesized as a pro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00077-07
更新日期:2007-07-01 00:00:00
abstract:UNLABELLED:Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures hav...
journal_title:Journal of virology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1128/JVI.00955-15
更新日期:2015-09-01 00:00:00
abstract::Retrovirus replication requires the production of both spliced and unspliced viral RNA from a single RNA transcript. In contrast, cellular RNA precursors with introns almost completely spliced. The cis elements and virus-coded trans factors which determine the extent to which Rous sarcoma virus RNA is spliced to src m...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1669-1676.1989
更新日期:1989-04-01 00:00:00
abstract::A radioimmunoassay (RIA) has been used to measure the quantity of protein P27 (mol wt 27,000; group specific-1 [gs-1]) of avian leukoviruses in different types of chicken embryos and tissues of adult chickens. The RIA used was 200- to 300-fold more sensitive than the complement fixation test and was able to detect as ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.2.340-346.1974
更新日期:1974-02-01 00:00:00
abstract::Rhesus rhadinovirus (RRV) is a gammaherpesvirus closely related to Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus linked to the development of Kaposi's sarcoma and several other lymphoproliferative diseases, including primary effusion lymphoma and multicentric Castleman's disease. RRV naturally inf...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01429-10
更新日期:2010-11-01 00:00:00
abstract::RNA plant viruses use various translational regulatory mechanisms to control their gene expression. Translational enhancement of viral mRNAs that leads to higher levels of protein synthesis from specific genes may be essential for the virus to successfully compete for cellular translational machinery. The control elem...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.3.1144-1153.2002
更新日期:2002-02-01 00:00:00
abstract::Endocytosis and endosomal trafficking regulate the proteins targeted to the plasma membrane and play essential roles in diverse cellular processes, including responses to pathogen attack. Here, we report the identification of Glycine max (soybean) endocytosis dynamin-like protein 5A (GmSDL5A) associated with purified ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01320-18
更新日期:2018-11-12 00:00:00
abstract::Arenaviruses are rodent-borne viruses, with five members of the family capable of causing severe hemorrhagic fevers if transmitted to humans. To date, two distinct cellular receptors have been identified that are used by different pathogenic viruses, alpha-dystroglycan by Lassa fever virus and transferrin receptor 1 (...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01397-07
更新日期:2008-01-01 00:00:00
abstract::Homo-oligomeric runs were inserted into a spleen necrosis virus-based retrovirus vector to determine the nature and rate of mutations within runs of 10 to 12 identical nucleotides during a single replication cycle. Clones of helper cells containing integrated copies of retroviral vectors were used to produce virus for...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.7.4196-4203.1994
更新日期:1994-07-01 00:00:00
abstract::Hepatitis C virus (HCV) is a single-stranded positive-sense RNA hepatotropic virus. Despite cellular defenses, HCV is able to replicate in hepatocytes and to establish a chronic infection that could lead to severe complications and hepatocellular carcinoma. An important player in subverting the host response to HCV in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00880-17
更新日期:2017-08-24 00:00:00
abstract::We have been studying defective interfering (DI) genomes of the RNA enveloped virus Sindbis virus. Deletion mapping of a DI cDNA demonstrated that only sequences at the 3' and 5' termini of the genome are required for the DI RNA to be biologically active. We constructed a series of cDNAs that transcribe DI RNAs differ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.1.47-53.1988
更新日期:1988-01-01 00:00:00
abstract::Fanconi anemia (FA) patients have an increased risk for squamous cell carcinomas (SCCs) at sites of predilection for infection with high-risk human papillomavirus (HPV) types, including the oral cavity and the anogenital tract. We show here that activation of the FA pathway is a frequent event in cervical SCCs. We fou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01121-07
更新日期:2007-12-01 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::Latency-associated transcript (LAT) promoter deletion mutants of herpes simplex virus type 1 have a reduced capacity to reactivate following adrenergic induction in the rabbit eye model. We have mapped a reactivation phenotype within LAT and describe the construction of recombinants in which poly(A) addition sites hav...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.4.2449-2459.1996
更新日期:1996-04-01 00:00:00
abstract::The genomic RNA 3' noncoding region is believed to be a major cis-acting molecular genetic determinant for regulating picornavirus negative-strand RNA synthesis by promoting replication complex recognition. We report the replication of two picornavirus RNAs harboring complete deletions of the genomic RNA 3' noncoding ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8868-8874.1997
更新日期:1997-11-01 00:00:00
abstract::Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01679-14
更新日期:2014-10-01 00:00:00