Many mBiosphere readers will know that the influenza A virus infects multiple species, and this ability to infect birds, humans, and other mammals such as pigs is one of the ways virions can exchange genetic information, leading to new viruses able to cause major outbreaks. However, few mBiosphere readers will think of cats as one of the major carriers of influenza virus, yet a New York Times article reports that a feline influenza outbreak is ongoing at a Queens shelter where about 500 cats—all of the cats from the entire New York City shelter system—are quarantined
Viral tropism is determined in part by the ability of the virus to attach to host cells, a property largely determined by the hemagglutinin (HA, or H) glycoprotein of the viral envelope (see image, right). The influenza viruses that circulate in humans are generally different than those that circulate in birds: the major circulating human viruses have H3 or H1, while the major circulating avian viruses that have been observed infecting people include H5, H7, and H9. When an avian-circulating virus jumps into the human population, the naivety of peoples’ immune systems to the new HA presents the potential to cause widespread disease; thus the basis for fear of an avian influenza. Fortunately, viruses that jump from birds to people are often not adapted to infect other people, and the infection becomes a dead-end for that virus.
An influenza virion schematic depicts the HA glycoproteins in blue and NA in red. Source.
The cat shelter outbreak represents an outlier scenario: the avian H7 influenza virus at the heart of the outbreak appears easily transmittable between cats. This particular virus, an H7N2 strain, is a virus with low pathogenicity: it causes disease in both animals and people, but with less-severe symptoms (e.g., less lung inflammation) and lower mortality than the highly pathogenic influenza viruses. One of the unique features of some H7 influenza viruses seems to be a lower barrier to interspecies transmission than that of other hemagglutinin types.
This was the conclusion of a recent Journal of Virology study that investigated the ability of 30 different low-pathogenicity H7 virus isolates to cause disease in a murine model. These isolates came from wild birds and were collected throughout the United States and Canada. Normally, avian influenza viruses must be adapted by serial passaging in mice before pathogenic virions are selected for and the viral infection results in disease. From the 30 H7 isolates tested however, 27 caused mortality in mice without prior adaptation.
Hemaglutinin acts as the initial viral attachment protein and binds preferentially to host cell proteins that have been modified with sialic acid. Birds and mice sialylate their epithelial cell proteins differently, and this difference affects the initial viral-host interactions. Avian viruses have higher affinity for avian α2,3-linked sialic acids, while mammalian viruses have higher affinity for mammalian α2,6-linked sialic acids. The H7 viruses studied had a preference for α2,3-linked sialic acids but were also capable of binding α2,6-linked sialic acids, a property that allow some H7 viruses to jump more easily between avian and mammalian infection. Affinity for different linkages was not affected by variants of neuraminidase (NA), another influenza glycoprotein.
What does this mean for the H7N2 influenza virus ability to infect humans? While no studies have been performed with this specific isolate, humans, like mice, have α2,6-linked sialic acids in their upper respiratory tract and people are susceptible to H7N2 infection. But jumping into and causing infection in a new species requires adaptation to multiple environmental factors, of which only one is the ability to bind to a new host receptor. Microbes must adapt to new host temperatures, available nutrients, immune defenses, and other factors that can limit microbial reproduction and infection. These multiple barriers are likely the reason that of 350 people exposed during the feline outbreak, only a single case of infection and disease has been documented so far.
The ability of any new virus to enter into a naive population is potentially dangerous, but because this is a low- pathogenicity avian influenza virus, the threat of serious disease to most healthy individuals is low. However, avoiding infection is the best way to protect vulnerable populations such as the very young and the elderly, whose immune systems might not fight off infection as effectively. The H7N2 virus wasn’t included in the 2016-17 influenza vaccine, so the best way to avoid spreading disease if exposed is to avoid infection by washing your hands frequently and avoiding touching your face (and in the case of the animal shelter workers, wearing personal protective equipment when handling cats).
Cat owners, take heart! Though the source of the H7N2 virus hasn’t been determined, so far only the Queens shelter has been identified as positive for the virus, and spread has been halted through quarantine of sick animals. With luck, the preventative measures taken by the authorities will prevent any further cases in cats or in their human caretakers.