Influenza H5 virus escape mutants: immune protection and antibody production in mice

被引：19

作者：

Smirnov, YA ^{[1
]}

Gitelman, AK ^{[1
]}

Govorkova, EA ^{[1
]}

Lipatov, AS ^{[1
]}

Kaverin, NV ^{[1
]}

机构：

[1] RAMS, DI Ivanovskii Virol Inst, Moscow 123098, Russia

来源：

VIRUS RESEARCH | 2004年 / 99卷 / 02期

关键词：

influenza A virus; escape mutants; hemagglutinin; immune protection; antibody induction;

D O I：

10.1016/j.virusres.2003.11.012

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Avian H5N1 influenza A viruses are considered to be of high pandemic potential as they are able to cross the avian-human species barrier and cause disease in humans. In the present study we assessed the impact of amino acid substitutions in the hemagglutinin (HA) of antigenic escape mutants of influenza A/Mallard/Pennsylvania/10218/84 (H5N2) (Mld/PA/84-MA) virus on the level of neutralizing antibodies and the ability to protect mice against challenge with the wild type H5 influenza virus. beta-Propiolactone-inactivated vaccines prepared from eight different H5 escape mutants could be separated into two groups based on levels of protection. One group of escape mutants [m46(7), m46(7)-24B9, m46(7)-55, and m46(7)-55-24B9] was characterized by providing high levels of protection (90.0-95.4% survival) to mice against subsequent challenge with 5 LD50 of wild type Mld/PA/84-MA virus. The other group of escape mutants [m176/26, m55(2), m55(2)-24B9, and m24B9-176/26] provided moderate level of protection (57.1-66.6% survival) in mice. Analysis of the amino acid substitutions in the HA revealed that two amino acid changes in antigenic site B of the HA molecule (D-126-->N and K-152-->N) were associated for decreases in the levels of antibody and the immune protection afforded by vaccination with these H5 virus escape mutants. The phenotypic effects of mutations in HA gene of H5 virus may be of importance to appraise the extent and direction of H5 influenza viruses antigenic evolution. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：205 / 208

页数：4

共 21 条

[1] Genetic analysis of mouse-adapted influenza A virus identifies roles for the NA, PB1, and PB2 genes in virulence [J].

Brown, EG ;

Bailly, JE .

VIRUS RESEARCH, 1999, 61 (01) :63-76

[2] Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: Identification of functional themes [J].

Brown, EG ;

Liu, H ;

Kit, LC ;

Baird, S ;

Nesrallah, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (12) :6883-6888

[3] PRINCIPLES OF SELECTIVE INACTIVATION OF VIRAL GENOME .8. THE INFLUENCE OF BETA-PROPIOLACTONE ON IMMUNOGENIC AND PROTECTIVE ACTIVITIES OF INFLUENZA-VIRUS [J].

BUDOWSKY, EI ;

SMIRNOV, YA ;

SHENDEROVICH, SF .

VACCINE, 1993, 11 (03) :343-348

[4] THE ANTIGENIC STRUCTURE OF THE INFLUENZA-VIRUS A/PR/8/34 HEMAGGLUTININ (H-1 SUBTYPE) [J].

CATON, AJ ;

BROWNLEE, GG ;

YEWDELL, JW ;

GERHARD, W .

CELL, 1982, 31 (02) :417-427

[5] Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans [J].

Cauthen, AN ;

Swayne, DE ;

Schultz-Cherry, S ;

Perdue, ML ;

Suarez, DL .

JOURNAL OF VIROLOGY, 2000, 74 (14) :6592-6599

[6] Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus [J].

Claas, ECJ ;

Osterhaus, ADME ;

van Beek, R ;

De Jong, JC ;

Rimmelzwaan, GF ;

Senne, DA ;

Krauss, S ;

Shortridge, KF ;

Webster, RG .

LANCET, 1998, 351 (9101) :472-477

[7] A pandemic warning? [J].

deJong, JC ;

Claas, ECJ ;

Osterhaus, ADME ;

Webster, RG ;

Lim, WL .

NATURE, 1997, 389 (6651) :554-554

[8] Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR [J].

Guan, Y ;

Peiris, JSM ;

Lipatov, AS ;

Ellis, TM ;

Dyrting, KC ;

Krauss, S ;

Zhang, LJ ;

Webster, RG ;

Shortridge, KF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (13) :8950-8955

[9] Cross-protection and reassortment studies with avian H2 influenza viruses [J].

Kaverin, NV ;

Smirnov, YA ;

Govorkova, EA ;

Rudneva, IA ;

Gitelman, AK ;

Lipatov, AS ;

Varich, NL ;

Yamnikova, SS ;

Makarova, NV ;

Webster, RG ;

Lvov, DK .

ARCHIVES OF VIROLOGY, 2000, 145 (06) :1059-1066

[10] STUDIES ON THE GENETIC-BASIS OF HUMAN INFLUENZA-A VIRUS ADAPTATION TO MICE - DEGREES OF VIRULENCE OF REASSORTANTS WITH DEFINED GENETIC CONTENT [J].

KAVERIN, NV ;

FINSKAYA, NN ;

RUDNEVA, IA ;

GITELMAN, AK ;

KHARITONENKOV, IG ;

SMIRNOV, YA .

ARCHIVES OF VIROLOGY, 1989, 105 (1-2) :29-37

← 1 2 3 →