Pathogenesis and control of viruses that adversely affect avian gut health

 

 

Several different viruses have been identified as causes of intestinal tract disease in chickens and turkeys, and several others have been associated as causes based on electron microscopic identification in tissues and/or intestinal contents of affected poultry. Virus-induced enteric infections occur in birds of all age groups but tend to predominate in young birds. Clinically, these diseases result in a broad range of outcomes ranging from inapparent, economically insignificant effects to severe and economically devastating disease.

 

In today’s modern poultry production systems where feed represents the single largest monetary investment, these diseases invariably result in decreased efficiency of feed utilization, and this, by itself, may result in substantial economic loss. However, these virus infections often have other adverse effects on productivity, including increased mortality, decreased growth rates, decreased flock uniformity, and increased susceptibility to other infectious agents. Virus-induced damage may potentiate the pathogenesis of other infectious agents, including normal gut microflora.

 

These infections also may result in nutritional deficiencies.

 

 

Virus-induced enteric disease in chickens and turkeys may be produced by viruses that target differentiated enterocytes that cover intestinal villi (e.g. coronavirus, rotavirus) or by parvoviruses that target the crypts of Lieberkuhn. Alternatively, the avian adenovirus, hemorrhagic enteritis virus (HEV) produces enteritis by damaging cells within the lamina propria of intestinal villi.

 

Viruses that replicate in differentiated villous enterocytes include rotavirus, coronavirus, and astrovirus. Based on experimental studies, these viruses, by themselves, typically produce only mild disease; however, naturally-occurring enteric diseases commonly are complicated by other cofactors including other infectious agents and nutrition. Experimental challenge studies conducted in laboratory settings often fail to provide a clear understanding of the role of these viruses in naturally-occurring disease, as these studies do not duplicate field conditions (i.e. environmental, management, nutrition and microbial flora). Thus, diseases such as malabsorption syndrome, runting/stunting syndrome, poult enteritis, and poult enteritis-mortality syndrome, which likely are multifactorial in nature, generally cannot be reproduced with only viruses.

 

Differentiated villous enterocytes are nonproliferating cells that have both absorptive and digestive functions (3). In contrast, crypt enterocytes are undifferentiated cells that are the progenitors of villous enterocytes; these cells actively secrete fluid into the intestinal lumen. In health, the absorptive capacity of the villous enterocytes exceeds the secretory capacity of crypt enterocytes, thus net absorption occurs along the villous surface. Virus infection and consequent damage of villous enterocytes disrupt this balance by reducing the surface area of the gut mucosa (villous atrophy) and by altering the function of individual villous enterocytes. These effects lead to a generalized reduction in digestive and absorptive capacity; functional deficits that are referred to as malabsorption and maldigestion. These functional deficits are complicated by osmotic effects in which undigested and unabsorbed feed remains in the intestinal lumen and acts to hold water. Bacterial fermentation of these unabsorbed food particles results in production of additional osmotically-active, low-molecular weight molecules that further increase the retention of water in the lumen of the intestinal tract. Unabsorbed fluids are passed down the intestinal tract to the large intestine; diarrhea results when the absorptive capacity of the large intestine is exceeded. These effects, by themselves, likely are common and economically-important sequela of intestinal infections caused by most viruses.

 

Virus-induced damage of villous enterocytes also may result in enteritis by potentiating the pathogenesis of other infectious agents, including normal gut microflora. While this is a likely pathogenic mechanism of virus-induced intestinal diseases of chickens and turkeys, it has received little attention. Virus-induced enterocyte damage may provide a portal of entry for other enteric pathogens such as Escherichia coli and Salmonella spp. Alternatively, virus-induced enterocyte damage may alter the intestinal luminal environment, and this may lead to perturbations of normal gut microflora.

 

Previous investigations have demonstrated synergistic interactions between rotavirus and enterotoxigenic E. coli in virus-induced enteric diseases of mammalian species (2); however, little work has been done to evaluate interactions of viruses and other infectious agents in the pathogenesis of enteritis in poultry. Turkey coronavirus has been shown to enhance intestinal colonization of enteropathogenic E. coli (EPEC) in young turkeys, and this combination of pathogens has been proposed as an etiological explanation for PEMS (1). It is interesting to speculate that other enteric diseases of poultry of unknown or poorly understood etiology (e. g. poult enteritis, runting/stunting syndrome of chickens) may ultimately be explained by interaction of viruses and other infectious agents.

 

The role of nutrition in the pathogenesis of virus-induced enteric diseases of poultry has received little attention. However, based on human and mammalian animal studies, it is likely that poor nutrition and poor feed quality contribute to severity of virus-induced enteric diseases. Studies of rotavirus infection in malnourished humans and laboratory animal models have demonstrated that malnutrition exacerbates severity and prolongs duration of clinical disease, by impairing rotavirus immune responses (4, 6). The influence of particular components of poultry diets, such as fat content, and presence of noxious compounds (e. g. rancid fat, mycotoxins) on virus enteric infections in poultry has not been examined.

 

The mechanism by which HEV causes intestinal disease and hemorrhage has not been conclusively determined. Unlike the enteric viruses discussed above, HEV does not replicate in villous enterocytes or crypt epithelium. Experimental studies indicate that HEV infection results in release of large quantities of proinflammatory cytokines, most importantly tumor necrosis factor, and this initiates systemic shock, leading to development of vascular lesions in the intestines (5). Such cytokine-induced vascular damage in the lamina propria leads to necrosis of villous tips and intestinal hemorrhage.

 

Control of viruses associated as causes of intestinal diseases of chickens and turkeys is best accomplished by maintaining premises free of these agents. Transmission of these viruses generally occurs by the fecal-oral route; flock-to-flock spread most commonly occurs mechanically via movement of people and equipment. Contaminated litter is the most likely source of infection for susceptible flocks, as well as for maintaining infection on contaminated premises.

 

Immunization, a favored method for controlling viral infections, has been useful only for HEV infections of turkeys. Vaccination by the drinking water may be done using naturally-occurring, attenuated strains of HEV, or a closely-related virus called marble spleen disease virus.

 

Turkey coronavirus is successfully controlled in turkey populations based on eradication. Turkey coronavirus is readily inactivated by most common disinfectants. Successful eradication of this virus requires the identification of infected flocks. Elimination from contaminated premises then may be accomplished via depopulation followed by thorough cleaning and disinfection.

 

Astroviruses, reoviruses, rotaviruses, and parvoviruses are relatively resistant to inactivation and are excreted in feces in large numbers. They may survive in litter and on contaminated equipment for prolonged periods of time and this may be the primary source of infection for subsequent poultry flocks. Specific control procedures for these viruses have not been developed; control is aimed at ensuring thorough cleaning and disinfection of facilities between flocks, in order to reduce environmental contamination and degree of exposure of young poultry.

 

1. Guy, J. S., Smith, L. G., Breslin, J. J., Vaillancourt, J. P., and Barnes H. J. (2000) High mortality and growth depression experimentally produced by dual infection with enteropathogenic Escherichia coli and turkey coronavirus. Avian Diseases 44, 105-113.

2. Marshall, J. A. (2002) Mixed infections of intestinal viruses and bacteria in humans. In: Polymicrobial diseases. Brogden, K. and Guthmiller, J, eds. ASM Press, Washington, DC, USA, pp. 299-316.

3. Moon, H. W. (1978) Mechanisms in the pathogenesis of diarrhea: a review. Journal of the American Veterinary Medical Association 172, 443-448.

4. Offor, E., Riepenhoff-Talty, M., and Ogra, P. L. (1985). Effect of malnutrition on rotavirus infection in suckling mice: kinetics of early infection. Proceedings of the Society of Experimental Biology and Medicine 178, 85-90.

5. Rautenschlein, S., and Sharma, J. M. (2000) Immunopathogenesis of haemorrhagic enteritis virus (HEV) in turkeys. Developmental and Comparative Immunology 24, 237-246.

6. Zijlstra, R. T., McCracken, B. A., Odle, J., Donovan, S. M., Gelberg, H. B., Petschow, B. W., Zuckerman, F. A., and Gaskins, H. R. (1999) Malnutrition modifies pig small intestinal inflammatory responses. American Society of Nutritional Sciences 129, 838-843.