By Roberta Attanasio
In March 2013, a new flu virus — the H7N9 — was identified in China. By early May, before retreating and disappearing, it had infected 131 people and killed 26 of them. However, less than two weeks ago (January 17), the New York Times reported that “China is disclosing a steadily growing number of cases of H7N9 bird flu, including four more cases announced on Friday, reviving concerns among health experts that the disease may be spreading and could pose a further threat as the world’s largest annual human migration begins ahead of Chinese New Year.”
The H7N9 virus is a “reassortant” — it includes combined elements from three distinct viruses. People acquire the virus mostly from exposure to infected poultry. As of today (January 29, 2013), the World Health Organization states that there is no evidence of sustained person-to-person spread of H7N9. No cases of H7N9 infection have been reported outside of China.
According to the Centers for Disease Control and Prevention (CDC), “It’s likely that sporadic cases of H7N9 associated with poultry exposure will continue to occur in China. Cases associated with poultry exposure also may be detected in neighboring countries. It’s also possible that H7N9 may be detected in the United States at some point, possibly in a traveler returning from an affected area. Most concerning about this situation is the pandemic potential of this virus.”
During pandemics, which are caused by the worldwide spread of infectious microbes, different human populations respond differently to the infection, most likely because of specific differences in factors related to their immune system.
Is this also true for the H7N9 virus? Should we expect differences in the susceptibility of different populations to infection?
An international team of investigators from institutions in Australia, Singapore, the U.S. and the U.K. report, in an article recently published by the journal Proceedings of the National Academy of Sciences USA (January 21, 2014), that different human populations may indeed vary in their susceptibility to H7N9 infection. The article is titled “Preexisting CD8+ T-cell immunity to the novel H7N9 influenza A virus varies across ethnicities” and presents results related to several ethnic groups, including Caucasoid, North American natives, Oriental, African, Amerindian, Alaskan Yupik and Australian Aboriginals.
Because H7N9 is a “new” virus, the immune system does not have memory of it and it is not ready to quickly produce neutralizing antibodies — which protect from infection or severe disease — when it encounters the virus. In absence of neutralizing antibodies, the human immune system relies mostly on a type of killer cells — called cytotoxic T lymphocytes — for protection against the virus. These lymphocytes kill cells infected with the virus along with the virus growing in them.
However, cytotoxic T lymphocytes can kill infected cells only if viral peptides — short segments of the viral proteins — are bound, in the infected cells, to molecules called HLA. Many of the peptides from the H7N9 flu virus are very similar (“conserved”) to peptides from other flu viruses with which human populations have already been in contact, and cytotoxic T lymphocytes that “remember” these peptides are ready to kill cells infected by H7N9.
There is a caveat, though. HLA molecules are present in the human population in a very large number of variants, and not all variants are able to bind the same peptides. Consequently, some human populations may not have HLA molecules that bind H7N9 peptides and, therefore, may not use quick-acting cytotoxic T lymphocytes to eliminate the virus.
Results from the study show that Alaskan and Australian Indigenous people do not have HLA variants able to bind the “conserved” H7N9 peptides and, therefore, may be particularly vulnerable to H7N9 infection.