Avian Influenza Virus In Mammals Spreads Beyond The Site Of Infection To Other Organ Systems

Avian influenza (H5N1) is of great concern because of the current outbreaks in Asia and the potential for pandemic spread. This virus is highly contagious in birds and spreads easily due to the agricultural and migratory nature of the bird species infected, including poultry, water fowl, and other migratory species (See commentary by Brown for more information). While spread of avian influenza from bird to man is known to occur, as first reported during the 1997 Hong Kong outbreak, human-to-human spread is extremely rare. Thus, the disease events that take place during mammal-to-mammal spread are not well characterized.

To assess the spread of H5N1 influenza virus in mammalian hosts, Rimmelzwaan et al. examined cats infected via the respiratory tract, via the digestive tract (by feeding on infected chicks), or by close contact with respiratory-infected cats. The researchers, led by Dr. Thijs Kuiken, then examined mucous membranes (throat, nasal, and rectal swabs) and organ systems (respiratory, digestive, nervous, cardiovascular, urinary, lymphoid, and endocrine) for the presence of virus and viral protein.

As expected, all cats were infected with H5N1 virus and exhibited clinical signs of disease (fever, lethargy, labored breathing, etc.), and virus was detected in throat, nasal, and rectal swabs, regardless of the original site of infection. Most interesting, virus spread throughout the organ systems with virus being found in respiratory and digestive tracts, liver, kidney, heart, brain, and lymph nodes. Furthermore, examination of infected tissues revealed cellular damage at sites containing viral proteins, providing an explanation for the increased severity of disease in humans.

These data underscore the potential for influenza virus to spread not only from the respiratory tract but also from the digestive and urinary tracts, greatly increasing the possible routes of mammalian transmission. Systemic disease has long been known to occur in birds, with the fecal-oral route of transmission being most important. However, this is the first demonstration of systemic replication in cats, providing a cautionary tale for humans regarding how influenza is spread and how the disease presents itself.

Rimmelzwaan and colleagues caution that because of the systemic nature of avian influenza, "H5N1 virus infection needs to be included in the differential diagnosis of a broader range of clinical presentations than is currently done." In addition better understanding of the mechanisms of spread, including possible fecal-oral route in humans, "may limit the risk of H5N1 virus developing into a pandemic influenza virus."

This work was performed at the Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands, and was supported by a Novaflu EU grant.

Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RAM, Osterhaus ADME, and Kuiken T: Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol 2006 168: 176-183.

Commentary: Brown C: Avian influenza: Virchow's reminder. Am J Pathol 2006 168: 6-8.

The American Journal of Pathology, the official journal of the American Society for Investigative Pathology (ASIP), seeks to publish high-quality original papers on the cellular and molecular mechanisms of disease. The editors accept manuscripts which report important findings on disease pathogenesis or basic biological mechanisms that relate to disease, without preference for a specific method of analysis. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, biological, animal, chemical and immunological approaches in conjunction with morphology.