Questions & Answers: H5N1 Genetic Changes Inventory

What is the H5N1 Genetic Changes Inventory? Why is it needed?

Highly pathogenic avian influenza (HPAI) H5N1 viruses mainly infect birds and are highly contagious among them, but sporadic infections of HPAI H5N1 viruses in humans also have occurred, causing serious illness, hospitalizations and deaths. The H5N1 Inventory is a list of naturally-occurring changes in the genetic makeup of H5N1 influenza viruses that may affect how these viruses infect and spread in mammalian hosts (including humans), or whether these viruses become resistant to influenza antiviral drugs. The Centers for Disease Control and Prevention (CDC) and other health organizations, such as the World Health Organization (WHO), World Organization for Animal Health (WOAH), and Food and Agriculture Organization of the United Nations (FAO), perform surveillance to monitor for genetic changes in the viruses that could increase the threat to human health. CDC researchers led a group of international influenza experts in the compilation of the H5N1 Inventory, a tool to help those conducting influenza surveillance and research identify specific genetic changes in naturally-occurring H5N1 viruses that may threaten human health.

Why is it important to monitor highly pathogenic avian influenza H5N1 viruses?

HPAI H5N1 influenza viruses, like all influenza A viruses, are constantly changing. Since they were first detected in humans in 1997, H5N1 influenza viruses have evolved into different genetic groups or “clades.” Some genetic changes may help H5N1 viruses become more transmissible—or more capable of spreading and causing serious illness in humans and animals. When novel influenza viruses become more transmissible in humans and there is little to no immunity to them in the human population, an influenza pandemic may occur. Other genetic changes may cause H5N1 viruses to become resistant to antiviral drugs. CDC and other health organizations around the world closely monitor genetic changes that could have implications for animal and public health.

Does CDC “keep track” of genetic changes in HPAI H5N1 viruses?

To improve pandemic preparedness and aid the influenza surveillance and research community, CDC has compiled an inventory of H5N1 virus genetic changes that may impact the transmissibility of these viruses and/or their susceptibility to influenza antiviral drugs. Influenza researchers can use this resource to identify genetic changes in H5N1 viruses that may have a significant public health impact. It is recognized that the H5N1 Inventory will need to be updated periodically, as H5N1 viruses continue to evolve. CDC will update this inventory on a regular basis in partnership with international influenza experts.

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What kind of genetic changes are included in H5N1 inventory?

Genetic changes occur that affect the amino acid sequence of the proteins of the viruses. These changes in amino acids affect properties of proteins—such as hemagglutinin (HA) or neuraminidase (NA), the surface proteins of influenza viruses. Genetic changes in amino acids—the substitution of one amino acid for another—can affect the properties of a virus such as how well a virus grows, how well it transmits between hosts or its susceptibility to antiviral drugs. Influenza researchers conduct a range of studies that look at how genetic changes influence certain properties of H5N1 influenza viruses. The inventory of amino acid changes in H5N1 influenza viruses helps researchers identify amino acid sequences that may increase pandemic potential.

How was the H5N1 Inventory developed?

A group of influenza subject matter experts compiled the H5N1 Inventory of amino acid changes in viruses’ genetic sequence or amino acid motifs (varying combinations of amino acid sequences) by: (1) conducting a literature review of published and publically available information on H5N1 genetic changes, and (2) using a text mining process that examined existing PubMed H5N1 publications for information about changes in the genetic makeup of H5N1 viruses. This information was then verified by other influenza subject matter experts.

How should the H5N1 inventory be used?

The inventory of H5N1 genetic changes is intended for use by researchers conducting influenza surveillance and research on H5N1 viruses in humans and animals. The H5N1 Inventory should be used as a reference for the identification of specific genetic changes in naturally-occurring H5N1 viruses that may indicate adaptation to mammalian species or altered susceptibility to existing influenza antiviral drugs. Because adaptation of H5N1 viruses to mammalian species may occur through multiple pathways, surveillance and research teams that identify viruses with multiple genetic changes should alert a relevant WHO Collaborating Center or an H5N1 reference laboratory and submit the virus for further characterization and for risk assessment. Contact information for these laboratories can be found at the Global Influenza Surveillance and Response System (GISRS).

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