IV Mutation Detail Information

Virus Mutation IV Mutation H274Y


Basic Characteristics of Mutations
Mutation Site H274Y
Mutation Site Sentence TABLE 1
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region HA
Standardized Encoding Gene HA
Genotype/Subtype H1N1;H5N1
Viral Reference EPI397889;EPI397888;EPI397887;EPI397892;EPI397891;EPI397890;EPI507529;EPI507528;EPI508430;EPI507531;EPI507530;EPI515738;EPI395306;EPI395305;EPI395302;EPI400083;EPI400085;EPI400084;EPI123515;EPI116648;EPI25613;EPI424370;EPI424369;EPI424365;EPI424378;EPI424377;EPI424373;EPI569383;EPI569385;EPI569386;EPI569390;EPI569392;EPI569393;EPI459855;EPI459857;EPI459858;EPI372512;EPI372511;EPI372507;EPI457483;EPI457482;EPI457478;EPI744942;EPI744941;EPI744940;EPI744945;EPI744944;EPI744943;EPI744948;EPI744947;EPI744946;EPI498037;EPI498036;EPI498032;EPI540159;EPI540158;EPI540154;EPI744935;EPI744934;NS;EPI744937;EPI744936;NS;EPI744939;EPI744938;NS;EPI407987;EPI407997;EPI407996;EPI828813;EPI828814;NS;EPI828815;EPI828816;NS;EPI746386;EPI244127;NS;EPI466983;EPI466982;EPI466981;EPI397961;EPI397960;EPI397957;EPI240428;NS;EPI240272;EPI243157;EPI243159;EPI243160;EPI744951;EPI744950;EPI744949;EPI744954;EPI744953;EPI744952;EPI439507;EPI439509;EPI439506;EPI744956;EPI503954;EPI744955;EPI439486;EPI439487;EPI439493;EPI515454;EPI503953;EPI515448;EPI516362;EPI503956;EPI516364;EPI498800;EPI498799;EPI498795;EPI744933;EPI744932;EPI744931;EPI372520;EPI372519;EPI372515;EPI184623;EPI184640;
Functional Impact and Mechanisms
Disease Influenza A    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location China
Literature Information
PMID 27630240
Title Human Monoclonal Antibody 81.39a Effectively Neutralizes Emerging Influenza A Viruses of Group 1 and 2 Hemagglutinins
Author Marjuki H,Mishin VP,Chai N,Tan MW,Newton EM,Tegeris J,Erlandson K,Willis M,Jones J,Davis T,Stevens J,Gubareva LV
Journal Journal of virology
Journal Info 2016 Nov 14;90(23):10446-10458
Abstract The pandemic threat posed by emerging zoonotic influenza A viruses necessitates development of antiviral agents effective against various antigenic subtypes. Human monoclonal antibody (hMAb) targeting the hemagglutinin (HA) stalk offers a promising approach to control influenza virus infections. Here, we investigated the ability of the hMAb 81.39a to inhibit in vitro replication of human and zoonotic viruses, representing 16 HA subtypes. The majority of viruses were effectively neutralized by 81.39a at a 50% effective concentration (EC(50)) of <0.01 to 4.9 mug/ml. Among group 2 HA viruses tested, a single A(H7N9) virus was not neutralized at 50 mug/ml; it contained HA(2)-Asp19Gly, an amino acid position previously associated with resistance to neutralization by the group 2 HA-neutralizing MAb CR8020. Notably, among group 1 HA viruses, H11-H13 and H16 subtypes were not neutralized at 50 mug/ml; they shared the substitution HA(2)-Asp19Asn/Ala. Conversely, H9 viruses harboring HA(2)-Asp19Ala were fully susceptible to neutralization. Therefore, amino acid variance at HA(2)-Asp19 has subtype-specific adverse effects on in vitro neutralization. Mice given a single injection (15 or 45 mg/kg of body weight) at 24 or 48 h after infection with recently emerged A(H5N2), A(H5N8), A(H6N1), or A(H7N9) viruses were protected from mortality and showed drastically reduced lung viral titers. Furthermore, 81.39a protected mice infected with A(H7N9) harboring HA(2)-Asp19Gly, although the antiviral effect was lessened. A(H1N1)pdm09-infected ferrets receiving a single dose (25 mg/kg) had reduced viral titers and showed less lung tissue injury, despite 24- to 72-h-delayed treatment. Taken together, this study provides experimental evidence for the therapeutic potential of 81.39a against diverse influenza A viruses. IMPORTANCE: Zoonotic influenza viruses, such as A(H5N1) and A(H7N9) subtypes, have caused severe disease and deaths in humans, raising public health concerns. Development of novel anti-influenza therapeutics with a broad spectrum of activity against various subtypes is necessary to mitigate disease severity. Here, we demonstrate that the hemagglutinin (HA) stalk-targeting human monoclonal antibody 81.39a effectively neutralized the majority of influenza A viruses tested, representing 16 HA subtypes. Furthermore, delayed treatment with 81.39a significantly suppressed virus replication in the lungs, prevented dramatic body weight loss, and increased survival rates of mice infected with A(H5Nx), A(H6N1), or A(H7N9) viruses. When tested in ferrets, delayed 81.39a treatment reduced viral titers, particularly in the lower respiratory tract, and substantially alleviated disease symptoms associated with severe A(H1N1)pdm09 influenza. Collectively, our data demonstrated the effectiveness of 81.39a against both seasonal and emerging influenza A viruses.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.