Feline Coronavirus Persistence in Healthy Cats

Kipar A, Meli ML, Baptiste KE, et al. Sites of feline coronavirus persistence in healthy cats. J Gen Virol March 17, 2010.

Feline coronavirus (FCoV), the agent of FIP, is transmitted by the fecal-oral route. Some cats infected with FCoV do not clear the virus, and shed the virus either persistently or intermittently. These cats are important sources of the virus in cat populations. These investigators examined the tissues of infected cats in order to identify the organ site of viral persistence in healthy carriers. Overall, the colon tested positive for virus more than any other tissue over time. Interestingly, all organs, including brain and skin, tested positive for virus in at least one cat during the investigatory period, indicating that FCoV infection disseminates to many organs during infection, even in healthy cats. Cats shedding the virus were found to be infected not only in the colon, but also in the small intestine (jejunum and ileum); in addition, the amount of virus present was an important determinant of shedding in feces, with higher amounts leading to viral shedding as one would expect. While the colon was the primary site for viral persistence and the source of continued shedding over the long-term, spread of the virus to the small intestines appears to be necessary for detectable fecal shedding. This would explain the intermittent nature of virus shedding in carrier cats. In addition, it was found that other tissues outside the gut may remain persistently infected as well, and could serve as a source for recurrent viremia. Most commonly, the mesenteric, or abdominal lymph nodes, and liver were sites of viral persistence. In these tissues, it appears that the resident macrophages are the specific cells involved. Thus, even cats that clear the virus from the intestines may remain virus-infected. [MK]

Related articles:
Goodson TL, Randell SC, Moore LE. Feline infectious peritonitis. Compend Contin Educ Vet 2009;31.

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Kipar A, Meli ML, Baptiste KE, et al. Sites of feline coronavirus persistence in healthy cats. J Gen Virol March 17, 2010.

Feline coronavirus (FCoV), the agent of FIP, is transmitted by the fecal-oral route. Some cats infected with FCoV do not clear the virus, and shed the virus either persistently or intermittently. These cats are important sources of the virus in cat populations. These investigators examined the tissues of infected cats in order to identify the organ site of viral persistence in healthy carriers. Overall, the colon tested positive for virus more than any other tissue over time. Interestingly, all organs, including brain and skin, tested positive for virus in at least one cat during the investigatory period, indicating that FCoV infection disseminates to many organs during infection, even in healthy cats. Cats shedding the virus were found to be infected not only in the colon, but also in the small intestine (jejunum and ileum); in addition, the amount of virus present was an important determinant of shedding in feces, with higher amounts leading to viral shedding as one would expect. While the colon was the primary site for viral persistence and the source of continued shedding over the long-term, spread of the virus to the small intestines appears to be necessary for detectable fecal shedding. This would explain the intermittent nature of virus shedding in carrier cats. In addition, it was found that other tissues outside the gut may remain persistently infected as well, and could serve as a source for recurrent viremia. Most commonly, the mesenteric, or abdominal lymph nodes, and liver were sites of viral persistence. In these tissues, it appears that the resident macrophages are the specific cells involved. Thus, even cats that clear the virus from the intestines may remain virus-infected. [MK]

Related articles:
Goodson TL, Randell SC, Moore LE. Feline infectious peritonitis. Compend Contin Educ Vet 2009;31.

More on cat health: Winn Feline Foundation Library
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Genetics of Feline Infectious Peritonitis Virus

Chang HW, de Groot RJ, Egberink HF et al.: Feline infectious peritonitis: insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene, J Gen Virol 91:415, 2010.

The virus of the lethal disease, feline infectious peritonitis (FIP), is closely related to the relatively innocuous form of feline coronavirus (FCoV). There is genetic and animal experimental evidence to indicate that the disease-causing form evolves time and time again from the harmless one by mutation in individual infected cats. What this specific mutation in the virus is remains unknown. One possible gene that may be involved, termed the “3c” gene, encodes a viral protein of unknown function. Previous studies have identified mutations in this gene that may be associated with FIP development. In this report, the investigators examined the 3c gene in the coronavirus infecting 27 healthy cats and 28 cats diagnosed with FIP in order to compare the viruses in this genetic region. Interestingly, the 3c gene in the virus of healthy cats was always intact, with no mutations. However, in cats with FIP, the majority (20/28) of viruses had mutations in this gene, varying from minor changes in a few amino acids to major changes leading to lack of function of the encoded protein. The researchers also tested the feces of cats with FIP for coronavirus. Virus was found in only 6 of 17 cats, indicating that in most cats with FIP, coronavirus has been cleared from the intestines and is only present in the tissues. In samples from 6 cats in which virus were detected, the 3c gene either had no mutations (5/6) or only one amino acid change (1/6). These investigators proposed the following scenario: Cats become infected by circulating virus that replicates in the gut. Replication in this compartment and efficient fecal shedding strictly require an intact viral 3c gene. A mutation in the virus occurs continually, one or more of which incidentally provides the virus with the ability to replicate in macrophages and monocytes, which then spread the – now FIPV – infection to organs throughout the body. Once in this new environment, virus propagation no longer requires the 3c gene; thus, mutations readily occur in the gene that may even improve the virus’ replication in tissue. The result is the disease feline infectious peritonitis. [MK]

Related articles:
Brown MA, Troyer JL, Pecon-Slattery J et al.: Genetics and pathogenesis of feline infectious peritonitis virus, Emerg Infect Dis 15:1445, 2009.

Pedersen NC: A review of feline infectious peritonitis virus infection: 1963-2008, Journal of Feline Medicine & Surgery 11:225, 2009.

More on cat health: Winn Feline Foundation Library
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New for 2010: subscribe to our e-newsletter

Chang HW, de Groot RJ, Egberink HF et al.: Feline infectious peritonitis: insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene, J Gen Virol 91:415, 2010.

The virus of the lethal disease, feline infectious peritonitis (FIP), is closely related to the relatively innocuous form of feline coronavirus (FCoV). There is genetic and animal experimental evidence to indicate that the disease-causing form evolves time and time again from the harmless one by mutation in individual infected cats. What this specific mutation in the virus is remains unknown. One possible gene that may be involved, termed the “3c” gene, encodes a viral protein of unknown function. Previous studies have identified mutations in this gene that may be associated with FIP development. In this report, the investigators examined the 3c gene in the coronavirus infecting 27 healthy cats and 28 cats diagnosed with FIP in order to compare the viruses in this genetic region. Interestingly, the 3c gene in the virus of healthy cats was always intact, with no mutations. However, in cats with FIP, the majority (20/28) of viruses had mutations in this gene, varying from minor changes in a few amino acids to major changes leading to lack of function of the encoded protein. The researchers also tested the feces of cats with FIP for coronavirus. Virus was found in only 6 of 17 cats, indicating that in most cats with FIP, coronavirus has been cleared from the intestines and is only present in the tissues. In samples from 6 cats in which virus were detected, the 3c gene either had no mutations (5/6) or only one amino acid change (1/6). These investigators proposed the following scenario: Cats become infected by circulating virus that replicates in the gut. Replication in this compartment and efficient fecal shedding strictly require an intact viral 3c gene. A mutation in the virus occurs continually, one or more of which incidentally provides the virus with the ability to replicate in macrophages and monocytes, which then spread the – now FIPV – infection to organs throughout the body. Once in this new environment, virus propagation no longer requires the 3c gene; thus, mutations readily occur in the gene that may even improve the virus’ replication in tissue. The result is the disease feline infectious peritonitis. [MK]

Related articles:
Brown MA, Troyer JL, Pecon-Slattery J et al.: Genetics and pathogenesis of feline infectious peritonitis virus, Emerg Infect Dis 15:1445, 2009.

Pedersen NC: A review of feline infectious peritonitis virus infection: 1963-2008, Journal of Feline Medicine & Surgery 11:225, 2009.

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Potential Treatment for FIP

Legendre, A.M. and J.W. Bartges, Effect of polyprenyl immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis. Journal of Feline Medicine & Surgery, 2009. 11(8): p. 624-626.

Feline infectious peritonitis (FIP) is a baffling and clinical important disease of cats caused by a virulent biotype of feline coronavirus. Despite the fact that the disease is relatively common, veterinarians are faced with a frustrating dilemma because there are no individual tests that are reliable for the diagnosis of FIP, the clinical picture is highly variable, and there is no known effective treatment. Polyprenyl immunostimulant (PI) is an investigational veterinary biologic manufactured by Sass & Sass, Inc and is comprised of a mixture of phosphorylated, linear polyisoprenols. This case series from the University of Tennessee describes three cats with the dry (non-effusive) form of FIP treated with PI. The cats were treated with varying doses of the drug, and by both subcutaneous and oral routes. Two of the three cats were still on treatment and were alive and well 2 years after diagnosis. The third cat survived 14 months but was treated for only 4.5 months. The investigators conclude that further studies to assess the therapeutic efficacy of PI for the treatment of FIP are warranted. [SL]
>> PubMed Abstract

Related Articles:
Addie, D., et al., Feline infectious peritonitis ABCD guidelines on prevention and management. J Feline Med Surg, 2009. 11(7): p. 594-604.
>> Full text article

Pedersen, N.C., A review of feline infectious peritonitis virus infection: 1963-2008. Journal of Feline Medicine & Surgery, 2009. 11(4): p. 225-258.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

Legendre, A.M. and J.W. Bartges, Effect of polyprenyl immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis. Journal of Feline Medicine & Surgery, 2009. 11(8): p. 624-626.

Feline infectious peritonitis (FIP) is a baffling and clinical important disease of cats caused by a virulent biotype of feline coronavirus. Despite the fact that the disease is relatively common, veterinarians are faced with a frustrating dilemma because there are no individual tests that are reliable for the diagnosis of FIP, the clinical picture is highly variable, and there is no known effective treatment. Polyprenyl immunostimulant (PI) is an investigational veterinary biologic manufactured by Sass & Sass, Inc and is comprised of a mixture of phosphorylated, linear polyisoprenols. This case series from the University of Tennessee describes three cats with the dry (non-effusive) form of FIP treated with PI. The cats were treated with varying doses of the drug, and by both subcutaneous and oral routes. Two of the three cats were still on treatment and were alive and well 2 years after diagnosis. The third cat survived 14 months but was treated for only 4.5 months. The investigators conclude that further studies to assess the therapeutic efficacy of PI for the treatment of FIP are warranted. [SL]
>> PubMed Abstract

Related Articles:
Addie, D., et al., Feline infectious peritonitis ABCD guidelines on prevention and management. J Feline Med Surg, 2009. 11(7): p. 594-604.
>> Full text article

Pedersen, N.C., A review of feline infectious peritonitis virus infection: 1963-2008. Journal of Feline Medicine & Surgery, 2009. 11(4): p. 225-258.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
Join us on Facebook

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Skin Lesions Associated with FIP

Declercq, J., H. De Bosschere, et al. (2008). "Papular cutaneous lesions in a cat associated with feline infectious peritonitis." Vet Dermatol 19(5): 255-8.

This paper describes unusual lesions associated with a case of feline infectious peritonitis (FIP)– slightly raised intradermal papules that were not painful nor itchy. The 7 month old intact male domestic shorthair cat also had other indicators of FIP, such as fever, anterior uveitis, respiratory distress, and kidney abnormalities. The skin lesions were on the neck and thorax and difficult to see in these haired areas. Histopathologic analysis of these lesions along with immunohistochemistry revealed typical FIP lesions. If detected early in the disease process, analysis of similar skin lesions may help provide a diagnosis. [MK]
>> PubMed Abstract

Related articles:
Cannon, M. J., M. A. Silkstone, et al. (2005). "Cutaneous lesions associated with coronavirus-induced vasculitis in a cat with feline infectious peritonitis and concurrent feline immunodeficiency virus infection." J Feline Med Surg 7(4): 233-6.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library
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Declercq, J., H. De Bosschere, et al. (2008). "Papular cutaneous lesions in a cat associated with feline infectious peritonitis." Vet Dermatol 19(5): 255-8.

This paper describes unusual lesions associated with a case of feline infectious peritonitis (FIP)– slightly raised intradermal papules that were not painful nor itchy. The 7 month old intact male domestic shorthair cat also had other indicators of FIP, such as fever, anterior uveitis, respiratory distress, and kidney abnormalities. The skin lesions were on the neck and thorax and difficult to see in these haired areas. Histopathologic analysis of these lesions along with immunohistochemistry revealed typical FIP lesions. If detected early in the disease process, analysis of similar skin lesions may help provide a diagnosis. [MK]
>> PubMed Abstract

Related articles:
Cannon, M. J., M. A. Silkstone, et al. (2005). "Cutaneous lesions associated with coronavirus-induced vasculitis in a cat with feline infectious peritonitis and concurrent feline immunodeficiency virus infection." J Feline Med Surg 7(4): 233-6.
>> PubMed Abstract

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Immunity and Feline Infectious Peritonitis

Giordano, A. and S. Paltrinieri (2009). "Interferon-gamma in the serum and effusions of cats with feline coronavirus infection." Vet J 180(3): 396-8.

Investigators from the University of Milan studied and compared the quantity of interferon-gamma concentrations in the serum of clinically normal cats infected with feline coronavirus (FCoV) with the concentrations in the sera and effusions of cats with feline infectious peritonitis (FIP), a disease associated with infection with a mutated form of FCoV. Interferon-gamma is a cytokine and an important modulator of cell mediated immunity. Cats with strong cell mediated immunity (CMI) either do not become infected with FCoV or develop the non-effusive form of FIP. Investigators divided cases into two major groups: Group A included cats with clinical FIP and Group B included FCoV infected clinically normal animals. Group A was further subdivided into two groups, those with non-effusive FIP (A1) and effusive FIP (A2). Group B was also subdivided into 2 groups where subgroup B1 included cats from catteries with a high prevalence of FIP and group B2 included cats from catteries with a low prevalence of FIP. Clinically normal FCoV-infected cats from catteries with a high prevalence of FIP had the highest level of serum interferon-gamma. The serum concentration of interferon-gamma was not significantly different in cats with FIP and the clinically normal FCoV-infected cats from catteries with a low prevalence of FIP. The effusions from cats with FIP had a significantly higher level (40 fold) of interferon-gamma than the serum in these cats. This suggests that cells within FIP lesions produce the interferon-gamma present in effusions. The investigators believe the results indicate that CMI is also likely to be involved in the pathogenesis of FIP, and interferon-gamma prevents the onset of FIP in some instances and could contribute to development of disease in others. [VT]
>> PubMed Abstract

Related articles:
Kipar, A., M. L. Meli, et al. (2006). "Natural feline coronavirus infection: differences in cytokine patterns in association with the outcome of infection." Vet Immunol Immunopathol 112(3-4): 141-55.
>> PubMed Abstract

Paltrinieri, S., C. Metzger, et al. (2007). "Serum alpha1-acid glycoprotein (AGP) concentration in non-symptomatic cats with feline coronavirus (FCoV) infection." J Feline Med Surg 9(4): 271-7.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library

Giordano, A. and S. Paltrinieri (2009). "Interferon-gamma in the serum and effusions of cats with feline coronavirus infection." Vet J 180(3): 396-8.

Investigators from the University of Milan studied and compared the quantity of interferon-gamma concentrations in the serum of clinically normal cats infected with feline coronavirus (FCoV) with the concentrations in the sera and effusions of cats with feline infectious peritonitis (FIP), a disease associated with infection with a mutated form of FCoV. Interferon-gamma is a cytokine and an important modulator of cell mediated immunity. Cats with strong cell mediated immunity (CMI) either do not become infected with FCoV or develop the non-effusive form of FIP. Investigators divided cases into two major groups: Group A included cats with clinical FIP and Group B included FCoV infected clinically normal animals. Group A was further subdivided into two groups, those with non-effusive FIP (A1) and effusive FIP (A2). Group B was also subdivided into 2 groups where subgroup B1 included cats from catteries with a high prevalence of FIP and group B2 included cats from catteries with a low prevalence of FIP. Clinically normal FCoV-infected cats from catteries with a high prevalence of FIP had the highest level of serum interferon-gamma. The serum concentration of interferon-gamma was not significantly different in cats with FIP and the clinically normal FCoV-infected cats from catteries with a low prevalence of FIP. The effusions from cats with FIP had a significantly higher level (40 fold) of interferon-gamma than the serum in these cats. This suggests that cells within FIP lesions produce the interferon-gamma present in effusions. The investigators believe the results indicate that CMI is also likely to be involved in the pathogenesis of FIP, and interferon-gamma prevents the onset of FIP in some instances and could contribute to development of disease in others. [VT]
>> PubMed Abstract

Related articles:
Kipar, A., M. L. Meli, et al. (2006). "Natural feline coronavirus infection: differences in cytokine patterns in association with the outcome of infection." Vet Immunol Immunopathol 112(3-4): 141-55.
>> PubMed Abstract

Paltrinieri, S., C. Metzger, et al. (2007). "Serum alpha1-acid glycoprotein (AGP) concentration in non-symptomatic cats with feline coronavirus (FCoV) infection." J Feline Med Surg 9(4): 271-7.
>> PubMed Abstract

More on cat health: Winn Feline Foundation Library

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Diagnosis of FIP

Winn funded research

Kennedy, M. A., M. Abd-Eldaim, et al. (2008). "Evaluation of antibodies against feline coronavirus 7b protein for diagnosis of feline infectious peritonitis in cats." American Journal of Veterinary Research 69(9): 1179-1182.

Feline infectious peritonitis (FIP) is a lethal, complex, and clinically important disease of cats caused by feline coronavirus (FCoV). FCoV occurs in two biotypes: one that is virulent and causes FIP, and one that is nonvirulent. FIP occurs in an effusive form characterized by pleural effusion or ascites, as well as a granulomatous form that may affect several organs. No consistent genetic difference has been identified that can distinguish all virulent from nonvirulent FCoVs. As a result, antemortem diagnosis of FIP is difficult because no test that is specific and sensitive for the FIP virus is available. It has been suggested that the product of the 7b gene is a virulence factor. If expression of the 7b protein consistently leads to FIP, cats infected with virulent FCoV would be expected to have measurable antibodies against this protein, whereas cats infected with the nonvirulent FCoV would not. This would allow differentiation of cats infected with virulent FCoV from those infected with a nonvirulent strain. The purpose of this study was to determine specific antibody concentrations against the 7b protein in cats with FIP or other diseases and healthy cats. Serum samples from 95 cats submitted for various diagnostic tests as well as 20 samples from specific pathogen free cats used as negative controls were tested for antibodies against the 7b protein. Serum from cats with FIP had antibodies against the 7b protein. However, some healthy cats, as well as cats with other diseases, were seropositive for the 7b protein. The researchers conclude that seropositivity for the 7b protein is not specific for the FCoV virulent biotype or a diagnosis of FIP.
>> PubMed abstract

Related articles:
Hartmann, K., C. Binder, et al. (2003). "Comparison of different tests to diagnose feline infectious peritonitis." J Vet Intern Med 17(6): 781-90.
>> PubMed abstract

More on cat health: Winn Feline Foundation Library

Winn funded research

Kennedy, M. A., M. Abd-Eldaim, et al. (2008). "Evaluation of antibodies against feline coronavirus 7b protein for diagnosis of feline infectious peritonitis in cats." American Journal of Veterinary Research 69(9): 1179-1182.

Feline infectious peritonitis (FIP) is a lethal, complex, and clinically important disease of cats caused by feline coronavirus (FCoV). FCoV occurs in two biotypes: one that is virulent and causes FIP, and one that is nonvirulent. FIP occurs in an effusive form characterized by pleural effusion or ascites, as well as a granulomatous form that may affect several organs. No consistent genetic difference has been identified that can distinguish all virulent from nonvirulent FCoVs. As a result, antemortem diagnosis of FIP is difficult because no test that is specific and sensitive for the FIP virus is available. It has been suggested that the product of the 7b gene is a virulence factor. If expression of the 7b protein consistently leads to FIP, cats infected with virulent FCoV would be expected to have measurable antibodies against this protein, whereas cats infected with the nonvirulent FCoV would not. This would allow differentiation of cats infected with virulent FCoV from those infected with a nonvirulent strain. The purpose of this study was to determine specific antibody concentrations against the 7b protein in cats with FIP or other diseases and healthy cats. Serum samples from 95 cats submitted for various diagnostic tests as well as 20 samples from specific pathogen free cats used as negative controls were tested for antibodies against the 7b protein. Serum from cats with FIP had antibodies against the 7b protein. However, some healthy cats, as well as cats with other diseases, were seropositive for the 7b protein. The researchers conclude that seropositivity for the 7b protein is not specific for the FCoV virulent biotype or a diagnosis of FIP.
>> PubMed abstract

Related articles:
Hartmann, K., C. Binder, et al. (2003). "Comparison of different tests to diagnose feline infectious peritonitis." J Vet Intern Med 17(6): 781-90.
>> PubMed abstract

More on cat health: Winn Feline Foundation Library

Read More