Neutralization escape mutants of type A influenza virus are readily selected by antisera from mice immunized with whole virus: a possible mechanism for antigenic drift

Ten antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody[ratio ]other antibodies of [ges ]2·0[ratio ]1. The antiserum with the highest ratio (7·4[ratio ]1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of [ges ]1000 HIU/ml, and a low absolute titre of other antibodies ([les ]500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event.

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Effect of Vaccine Use in the Evolution of Mexican Lineage H5N2 Avian Influenza Virus

Journal of Virology ◽

10.1128/jvi.78.15.8372-8381.2004 ◽

2004 ◽

Vol 78 (15) ◽

pp. 8372-8381 ◽

Cited By ~ 252

Author(s):

Chang-Won Lee ◽

Dennis A. Senne ◽

David L. Suarez

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Herd Immunity ◽

Type A ◽

Antigenic Drift ◽

Highly Pathogenic ◽

Virus Shedding ◽

First Case ◽

Pathogenic Virus

ABSTRACT An outbreak of avian influenza (AI) caused by a low-pathogenic H5N2 type A influenza virus began in Mexico in 1993 and several highly pathogenic strains of the virus emerged in 1994-1995. The highly pathogenic virus has not been reported since 1996, but the low-pathogenic virus remains endemic in Mexico and has spread to two adjacent countries, Guatemala and El Salvador. Measures implemented to control the outbreak and eradicate the virus in Mexico have included a widespread vaccination program in effect since 1995. Because this is the first case of long-term use of AI vaccines in poultry, the Mexican lineage virus presented us with a unique opportunity to examine the evolution of type A influenza virus circulating in poultry populations where there was elevated herd immunity due to maternal and active immunity. We analyzed the coding sequence of the HA1 subunit and the NS gene of 52 Mexican lineage viruses that were isolated between 1993 and 2002. Phylogenetic analysis indicated the presence of multiple sublineages of Mexican lineage isolates at the time vaccine was introduced. Further, most of the viruses isolated after the introduction of vaccine belonged to sublineages separate from the vaccine's sublineage. Serologic analysis using hemagglutination inhibition and virus neutralization tests showed major antigenic differences among isolates belonging to the different sublineages. Vaccine protection studies further confirmed the in vitro serologic results indicating that commercial vaccine was not able to prevent virus shedding when chickens were challenged with antigenically different isolates. These findings indicate that multilineage antigenic drift, which has not been observed in AI virus, is occurring in the Mexican lineage AI viruses and the persistence of the virus in the field is likely aided by its large antigenic difference from the vaccine strain.

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Antigenic drift in type A influenza virus: Sequence differences in the hemagglutinin of Hong Kong (H3N2) variants selected with monoclonal hybridoma antibodies

Virology ◽

10.1016/0042-6822(79)90540-3 ◽

1979 ◽

Vol 98 (1) ◽

pp. 226-237 ◽

Cited By ~ 117

Author(s):

W.G. Laver ◽

G.M. Air ◽

R.G. Webster ◽

W. Gerhard ◽

C.W. Ward ◽

...

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Type A ◽

Antigenic Drift ◽

Virus Sequence

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Heterotypic immunity to influenza in ferrets

Infection and Immunity ◽

10.1128/iai.29.2.650-653.1980 ◽

1980 ◽

Vol 29 (2) ◽

pp. 650-653

Author(s):

R A Yetter ◽

W H Barber ◽

P A Small

Keyword(s):

Influenza Virus ◽

Type A ◽

Influenza Viruses ◽

Virus Shedding

Heterotypic immunity to influenza virus in ferrets operated against heterotypic influenza viruses but not heterologous viruses. Contrary to prior reports, the protection conferred lasted for at least 18 months. This type of immunity limited virus shedding but did not prevent infection. These results suggest that this phenomenon could play a role in determining the severity of infections caused by type A influenza viruses in humans.

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Neutralizing Epitopes and Residues Mediating the Potential Antigenic Drift of the Hemagglutinin-Esterase Protein of Influenza C Virus

Viruses ◽

10.3390/v10080417 ◽

2018 ◽

Vol 10 (8) ◽

pp. 417 ◽

Cited By ~ 5

Author(s):

Yoko Matsuzaki ◽

Kanetsu Sugawara ◽

Yuki Furuse ◽

Yoshitaka Shimotai ◽

Seiji Hongo ◽

...

Keyword(s):

Amino Acid ◽

3D Structure ◽

Three Dimensional ◽

Antigenic Site ◽

Antigenic Drift ◽

Receptor Binding Site ◽

Ann Arbor ◽

Influenza C Virus ◽

Escape Mutants ◽

Antigenic Epitopes

We mapped the hemagglutinin-esterase (HE) antigenic epitopes of the influenza C virus on the three-dimensional (3D) structure of the HE glycoprotein using 246 escape mutants that were selected by a panel of nine anti-HE monoclonal antibodies (MAbs), including seven of the C/Ann Arbor/1/50 virus and two of the C/Yamagata/15/2004 virus. The frequency of variant selection in the presence of anti-HE MAbs was very low, with frequencies ranging from 10−4.62 to 10−7.58 for the C/Ann Arbor/1/50 virus and from 10−7.11 to 10−9.25 for the C/Yamagata/15/2004 virus. Sequencing of mutant HE genes revealed 25 amino acid substitutions at 16 positions in three antigenic sites: A-1, A-2, and A-3, and a newly designated Y-1 site. In the 3D structure, the A-1 site was widely located around the receptor-binding site, the A-2 site was near the receptor-destroying enzyme site, and the Y-1 site was located in the loop on the topside of HE. The hemagglutination inhibition reactions of the MAbs with influenza C viruses, circulating between 1947 and 2016, were consistent with the antigenic-site amino acid changes. We also found some amino acid variations in the antigenic site of recently circulating strains with antigenic changes, suggesting that viruses that have the potential to alter antigenicity continue to circulate in humans.

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Development of a multiplex real-time PCR assay using SYBR Green 1 chemistry for simultaneous detection and subtyping of H9N2 influenza virus type A

Journal of Virological Methods ◽

10.1016/j.jviromet.2007.03.019 ◽

2007 ◽

Vol 144 (1-2) ◽

pp. 57-64 ◽

Cited By ~ 40

Author(s):

Wee Theng Ong ◽

Abdul Rahman Omar ◽

Aini Ideris ◽

Sharifah Syed Hassan

Keyword(s):

Influenza Virus ◽

Real Time ◽

Virus Type ◽

Real Time Pcr ◽

Simultaneous Detection ◽

Type A ◽

Sybr Green ◽

Pcr Assay ◽

H9n2 Influenza Virus

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Avian influenza and Newcastle disease virusindead chickens in markets in Dhaka, Bangladesh in 2011-2012

Bangladesh Veterinarian ◽

10.3329/bvet.v33i1.33308 ◽

2017 ◽

Vol 33 (1) ◽

pp. 8-15

Author(s):

LR Barman ◽

RD Sarker ◽

BC Das ◽

EH Chowdhury ◽

PM Das ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Newcastle Disease ◽

Rapid Test ◽

Type A ◽

Antigen Test ◽

Rt Pcr ◽

Test Kit ◽

Live Bird

A virological survey for avian influenza (AI) and Newcastle disease (ND) was conducted in two selected live bird markets (LBMs), namely Kaptan Bazar and Karwan Bazar in Dhaka city, Bangladesh from August 2011 to July 2012. A total of 513 dead chickens were collected. An immune-chromatographic rapid antigen test for Type A influenza virus and both conventional and real time RT-PCR were used for the detection and characterization of AI and ND viruses. All carcasses were first screened by the rapid antigen test kit and 93 were positive for Type A influenza virus. RT-PCR on a representative number of rapid antigen test positive samples (n = 24) confirmed the presence of Type A influenza virus and mostly H5 influenza virus (22 out of 24 tested samples). Influenza rapid test negative samples (n = 420) were subjected to routine necropsy. Heat stress, suffocation and physical injury were the most common cause of mortality (163 cases), followed by ND, suspected to be the cause of 85 deaths. On molecular investigation of these 85 samples, the presence of ND virus was confirmed in 59 and AI virus in 6; 15 were negative for both ND and AI viruses and 5 were unsuitable for investigation. Among the 59 ND confirmed cases 18 also contained AI virus. In summary, out of 513 carcasses 117 (22.81%) contained AI virus and 59 (11.50%) contained ND virus. Eighteen (3.51%) carcasses contained both AI and ND viruses. The findings suggest that both AI and ND should be considered as major threats to the poultry industry.Bangl. vet. 2016. Vol. 33, No. 1, 8-15

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A case of an elderly patient with acute kidney injury due to rhabdomyolysis from type A (H1N1 pdm) influenza virus infection

Nihon Kyukyu Igakukai Zasshi ◽

10.3893/jjaam.24.781 ◽

2013 ◽

Vol 24 (9) ◽

pp. 781-786

Author(s):

Takeo Matsuyoshi ◽

Yasusei Okada ◽

Hiroshi Inagawa ◽

Naoki Kojima ◽

Kazumasa Yamaguchi ◽

...

Keyword(s):

Elderly Patient ◽

Acute Kidney Injury ◽

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Kidney Injury ◽

Type A

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Evidence that mild or asymptomatic human H5N1 infections have not occurred in a Cambodian village with poultry infections

Weekly releases (1997–2007) ◽

10.2807/esw.11.36.03039-en ◽

2006 ◽

Vol 11 (36) ◽

Cited By ~ 1

Author(s):

Collective Influenza team (ECDC)

Keyword(s):

Influenza Virus ◽

Risk Factor ◽

Virus Type ◽

Household Survey ◽

Type A ◽

Population Based ◽

H5n1 Infection ◽

Human H5n1

A retrospective serologic and risk factor population-based household survey for influenza virus type A/H5N1 infection was carried out in a Cambodian village where there had been extensive poultry deaths attributed to A/H5N1

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