Crossing the Species Barrier

“I would appeal to countries to invest more resources to strengthen animal-disease surveillance. Look at the new diseases that emerged in the last 30 years. The majority came from animals.”

– Dr. Margaret Chan, Director General, World Health Organization in Newsweek

Animal influenza viruses do not infect humans on a regular basis. In fact, all influenza viruses usually have perfected their mechanisms to attach to the right receptors in a host family, such as birds or humans. Crossing the species barrier to infect another species, thus, requires specific changes that are not achieved easily. This page explains when and how influenza viruses jump from one animal to another and how humans come into the mix.

Tip: Read a telling example of how social and economic conditions can lead to increased animal-human transmission by the Washington Post’s Alan Sipress.

On this page...
  Human influenza »
  Animal influenza »
  Crossing the bridge »
  The trouble with co-infections »
  A sophisticated travel map—in viral genes »

Human influenza

Human influenza can be caused by three types of influenza: A, B, and C. All influenza viruses can infect humans, but influenza A has been the only virus responsible for past pandemics.

Previous human influenza pandemics have been caused by three subtypes of hemaglutinin (H)—H1, H2, and H3 and two subtypes of neuraminidase (N)—N1 and N2. Currently, H1 and H3 are the subtypes that cause human seasonal influenza worldwide each year.

Animal influenza

Influenza infects animals, but not all animals are equally affected. Animals such as swine, horses, mink, seals, cats (wild and domestic), whales and seals can be periodically infected.

Type A influenza affects birds and they carry all 16 known subtypes. Wildfowl and aquatic birds serve as the reservoir for this virus. Bird strains can infect humans and other animals, but many subtypes do not effectively replicate in humans.1
Type B influenza usually affects humans, although seals and ferrets can also be infected.
Type C influenza can infect dogs, pigs, and humans.

Crossing the bridge

Many infectious diseases cross the species barrier. In most cases, humans come into contact with the animal itself, animal excreta, or animal parts (e.g., feathers, meat), or an insect is the vector of transmission of the infective microorganism. Classic examples of these forms of disease transmission are Lyme disease, plague, and the rabies virus.2

Animal influenza viruses do not infect humans on a regular basis, and all influenza viruses usually show some receptor specificity for their hosts, be they birds or mammals.

Areas where birds, pigs, and humans live close together do, however, provide major opportunities for influenza viruses to step across the species barrier and infect other animals or humans. Once the bridge is crossed, the stage for the creation of new influenza viruses is set. (As explained in How Flu Viruses Change.)

The trouble with co-infections

Influenza viruses can change by reassortment and by accumulating mutations (antigenic drift). The segmented nature of the influenza genome permits a circulating seasonal human influenza to acquire new genes through reassortment (antigenic shift). Such events can occur when an individual is co-infected with a seasonal virus as well as an avian virus or a virus adapted to a mammalian host, such as swine.

Interactions between humans and infected animals also may allow for viral recombination or adaptation to a new organism by repeated infections with mutated viruses. Reassorted or mutated viruses can have genes or gene combinations that allow them to cross species barriers more easily and adapt to new hosts.3

A sophisticated travel map—in viral genes

Investigators have reported several examples of adapted or reassorted viruses. An H3N2, with genes derived from human, swine and avian viruses, became endemic in pigs in the United States after 1998. Because it was a mixture of three different strains, it is known as a “triple reassortant.” Later, that virus underwent additional reassortment and produced additional H3N2 viruses that were subsequently found in pigs, as well as H1N2 viruses isolated from pigs, turkeys, and wild ducks.4

Sequence analysis of two H3N2 isolates from turkeys revealed that the viruses were closely related to a swine H3N2 virus found in North Carolina in 2002. The turkey H3N2 viruses were used to infect other experimental animals. Mice, swine, turkeys, and quail were all successfully infected with the virus, demonstrating that the gene combinations in this H3N2 subtype permitted it to cross multiple species barriers.5 Such occurrences probably occur in nature, although the particular gene combinations have not been definitively determined.

Additional mechanisms for crossing species barriers include accumulation of mutations to produce adaptation. Viruses with multiple mutations are gradually better able to bind cellular receptors after repeated infection. H7N7 viruses have been found to be partially adapted to recognize particular components that are receptors preferred by human influenza viruses and present in the upper respiratory tract.6

Other selected examples of cross species transmission include:

H5N1, a virus that has crossed the species barrier (to humans) three times since 1997.
H7 subtypes have infected humans and other animals. Direct transmission of an avian H7 virus to a human first occurred in 1996, and outbreaks in poultry have been followed by human outbreaks among those culling infected animals.7


  1. World Health Organization, Avian influenza (“bird flu”), February 2006.

  2. Stefan Riedel, Crossing the species barrier: the threat of an avian influenza pandemic, Baylor University Center Proceedings 19 (January 2006): 16–20.

  3. Centers for Disease Control and Prevention, Avian Influenza, Nov. 18, 2005.

  4. Young K. Choi, Jee H. Lee, Gene Erickson, et al., “H3N1 influenza virus transmission from swine to turkeys”, Emerging Infectious Diseases 10 (December 2004): 2156-2160.

  5. Ibid.

  6. Jessica A. Belser, Carolyn B. Bridges, Jacqueline M. Katz, et al., “Past, present, and possible future human infection with influenza virus A subtype H7,” Emerging Infectious Diseases 15 (June 2009): 859-865.

  7. Ibid.