Inflammatory myopathy and myocarditis are relevant complications of natural feline immunodeficiency virus infection

Abstract

Inflammatory myopathy (IM) and myocarditis are relevant complications of human immunodeficiency virus (HIV) infection. IM has also been reported in adult cats with experimental feline immunodeficiency virus (FIV) infection. The present study investigated naturally FIV-infected cats for IM and myocarditis and further characterized the inflammatory processes and their potential pathogenesis. Snap-frozen skeletal muscle (quadriceps femoris (QF) and triceps brachii (TB) muscles) and myocardial samples from naturally FIV-infected cats and controls were examined histologically and by immunohistochemistry for leukocytes and FIV-p24-gag, and by quantitative reverse transcription PCR (qRT-PCR) for the relative transcription of inflammatory mediators. Sera from FIV antibody-positive cats were tested for anti-skeletal muscle autoantibodies by indirect immunofluorescence (IIF). Inflammatory infiltrates were observed in 9/31 (35%) QF and TB muscles and 11/30 (37%) myocardial samples from FIV-infected cats, frequently in combination. The infiltrates were dominated by T-cells, with rare B-cells and macrophages; several leukocytes harbored FIV-p24-gag. The T-cell count in the QF was positively correlated with the T-cell count in TB and myocardium. Skeletal muscle of FIV-positive animals showed significantly higher transcription of interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-17, and transforming growth factor-beta than the controls, whereas the myocardium exhibited significantly higher IL-17 and lower IL-13 mRNA levels. IIF showed anti-skeletal muscle autoantibodies in sera of FIV positive cats up to a dilution of 1:1000. The results show that natural FIV infection is frequently associated with IM and myocarditis and driven by T-cells, with Th1/Th17 polarization of the response. The presence of circulating anti-muscle autoantibodies suggests an underlying autoimmune pathogenesis.

Keywords

autoantibodies feline immunodeficiency virus FIV inflammatory myopathy myocarditis retrovirus Th1/Th17 polarization

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References

Annunziato

Romagnani

The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2015;135(3):626–635.

Ascherman

DP.

Animal models of inflammatory myopathy. Curr Rheumatol Rep. 2012;14(3):257–263.

Authier

Chariot

Gherardi

RK.

Skeletal muscle involvement in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART). Muscle Nerve. 2005;32(3):247–260.

Barbaro

Di Lorenzo

Grisorio

, et al. Cardiac involvement in the acquired immunodeficiency syndrome: a multicenter clinical-pathological study. AIDS Res Hum Retroviruses. 1998;14(12):1071–1077.

Becker

The changes in the T helper 1 (Th1) and T helper 2 (Th2) cytokine balance during HIV-1 infection are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers–a review and hypothesis. Virus Genes. 2004;28(1):5–18.

Colpitts

Caswell

Monteith

, et al. Cardiac gene activation varies between young and adult cats and in the presence of hypertrophic cardiomyopathy. Res Vet Sci. 2022;152:38–47.

Costagliola

Piegari

Otrocka-Domagala

, et al. Immunopathological features of canine myocarditis associated with Leishmania infantum infection. Biomed Res Int. 2016;2016:8016186.

Currie

Goldman

Caforio

ALP

, et al. Cardiac autoimmunity in HIV related heart muscle disease. 1998;79(6):599–604.

Dalakas

MC.

Retroviruses and inflammatory myopathies in humans and primates. Baillieres Clin Neurol. 1993;2(3):659–691.

10.

Dalakas

Illa

Monzon

Retrovirus-related neuromuscular diseases. In: Immunology of Neuromuscular Disease. Dordrecht, Netherlands: Springer Netherlands; 1994:255–288.

11.

Dean

Pedersen

NC.

Cytokine response in multiple lymphoid tissues during the primary phase of feline immunodeficiency virus infection. J Virol. 1998;72(12):9436–9440.

12.

de Martinis

Cardillo

Esposito

, et al. First identification of bovine hepacivirus in wild boars. Sci Rep. 2022;12(1):11678.

13.

Diehl

Mathiason-DuBard

O’Neil

, et al. Longitudinal assessment of feline immunodeficiency virus kinetics in plasma by use of a quantitative competitive reverse transcriptase PCR. J Virol. 1995;69(4):2328–2332.

14.

Dubowitz Victor Sewry

Oldfors Anders Lane

RJM.

Muscle Biopsy: A Practical Approach. St. Chicago, IL: Saunders; 2013.

15.

Evans

Levesque

Shelton

GD.

Canine inflammatory myopathies: a clinicopathologic review of 200 cases. J Vet Intern Med. 2004;18(5):679–691.

16.

Herskowitz

Ahmed-Ansari

Neumann

, et al. Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: a nonhistologic marker of myocarditis. J Am Coll Cardiol. 1990;15(3):624–632.

17.

Hiniker

Daniels

Margeta

T-cell-mediated inflammatory myopathies in HIV-positive individuals: a histologic study of 19 cases. J Neuropathol Exp Neurol. 2016;75(3):239–245.

18.

Huck

Okello

Mirembe

, et al. Role of natural autoantibodies in Ugandans with rheumatic heart disease and HIV. EBioMedicine. 2016;5:161–166.

19.

Iyer

Cheng

Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. 2012;32(1):23–63.

20.

Jin

Blair

Warunek

, et al. Regulatory T cells promote myositis and muscle damage in Toxoplasma gondii infection. J Immunol. 2017;198(1):352–362.

21.

Kipar

Leutenegger

Hetzel

, et al. Cytokine mRNA levels in isolated feline monocytes. Vet Immunol Immunopathol. 2001;78(3–4):305–315.

22.

Kitz

Fonfara

Hahn

, et al. Feline hypertrophic cardiomyopathy: the consequence of cardiomyocyte-initiated and macrophage-driven remodeling processes? Vet Pathol. 2019;56(4):565–575.

23.

Koh

C-H

Lee

Kwak

, et al. CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential. Exp Mol Med. 2023;55(11):2287–2299.

24.

Landon-Cardinal

Gallay

Dubourg

, et al. Expanding the spectrum of HIV-associated myopathy. J Neurol Neurosurg Psychiatry. 2019;90(11):1296–1298.

25.

Leutenegger

Mislin

Sigrist

, et al. Quantitative real-time PCR for the measurement of feline cytokine mRNA. Vet Immunol Immunopathol. 1999;71(3–4):291–305.

26.

Lundberg

De Visser

Werth

VP.

Classification of myositis. Nat Rev Rheumatol. 2018;14(5):269–278.

27.

Malbon

Meli

Barker

, et al. Inflammatory mediators in the mesenteric lymph nodes, site of a possible intermediate phase in the immune response to feline coronavirus and the pathogenesis of feline infectious peritonitis? J Comp Pathol. 2019;166:69–86.

28.

McHugh

Tansley

SL.

Autoantibodies in myositis. Nat Rev Rheumatol. 2018;14(5):290–302.

29.

Meng

, et al. Antiretroviral therapy normalizes autoantibody profile of HIV patients by decreasing CD33+ CD11b+ HLA-DR+ cells. Medicine (Baltimore). 2016;95(15):1–9.

30.

Miller

Lamb

Schmidt

, et al. Risk factors and disease mechanisms in myositis. Nat Rev Rheumatol. 2018;14(5):255–268.

31.

Moran

Mastaglia

FL.

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications. Clin Exp Immunol. 2014;178(3):405–415.

32.

Ntusi

NAB

. HIV and myocarditis. Curr Opin HIV AIDS. 2017;12(6):561–565.

33.

Paciello

Oliva

Gradoni

, et al. Canine inflammatory myopathy associated with Leishmania infantum infection. Neuromuscul Disord. 2009;19(2):124–130.

34.

Paciello

Papparella

Histochemical and immunohistological approach to comparative neuromuscular diseases. Folia Histochem Cytobiol. 2009;47(2):143–152.

35.

Pagano

Prisco

De Biase

, et al. Muscular sarcocystosis in sheep associated with lymphoplasmacytic myositis and expression of major histocompatibility complex class I and II. Vet Pathol. 2020;57(2):272–280.

36.

Pasolini

Pagano

Costagliola

, et al. Inflammatory myopathy in horses with chronic piroplasmosis. Vet Pathol. 2018;55(1):133–143.

37.

Podell

Inflammatory myopathies. Vet Clin North Am Small Anim Pract. 2002;32(1):147–167.

38.

Podell

Chen

Shelton

GD.

Feline immunodeficiency virus associated myopathy in the adult cat. Muscle Nerve. 1998;21(12):1680–1685.

39.

Prisco

De Biase

Piegari

, et al. Leishmania spp.-infected dogs have circulating anti-skeletal muscle autoantibodies recognizing SERCA1. Pathogens. 2021;10(4):463.

40.

Prisco

De Biase

Piegari

, et al. Pathologic characterization of white striping myopathy in broiler chickens. Poult Sci. 2021:101150.

41.

Prisco

Papparella

Paciello

The correlation between cardiac and skeletal muscle pathology in animal models of idiopathic inflammatory myopathies. Acta Myol. 2020;39(4):313–319.

42.

Rolim

Casagrande

Wouters

ATB

, et al. Myocarditis caused by feline immunodeficiency virus in five cats with hypertrophic cardiomyopathy. J Comp Pathol. 2016;154(1):3–8.

43.

Sani

MU.

Myocardial disease in human immunodeficiency virus (HIV) infection: a review. Wien Klin Wochenschr. 2008;120(3–4):77–87.

44.

Shannon

SIV cardiomyopathy in non-human primates. Trends Cardiovasc Med. 2001;11(6):242–246.

45.

Shelton

GD.

From dog to man: the broad spectrum of inflammatory myopathies. Neuromuscul Disord. 2007;17(9–10):663–670.

46.

Tabarkiewicz

Pogoda

Karczmarczyk

, et al. The role of IL-17 and Th17 lymphocytes in autoimmune diseases. Arch Immunol Ther Exp (Warsz). 2015;63(6):435–449.

47.

Taglinger

Van Nguyen

Helps

, et al. Quantitative real-time RT-PCR measurement of cytokine mRNA expression in the skin of normal cats and cats with allergic skin disease. Vet Immunol Immunopathol. 2008;122(3–4):216–230.

48.

Tien-Auh Chan

Kirton

Estanislao

, et al. Myopathy in HIV infection. Handb Clin Neurol. 2007;85(Actg016):139–145.

49.

Wang

Johnson

Ahluwalia

, et al. Dual-emission fluorescence resonance energy transfer (FRET) real-time PCR differentiates feline immunodeficiency virus subtypes and discriminates infected from vaccinated cats. J Clin Microbiol. 2010;48(5):1667–1672.

50.

World International Property Organization (WIPO). Quantitative polymerase chain reaction using a fluorogenic real-time detection system. WO/2000/037672, 2000. https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2000037672

51.

Yearley

Pearson

Carville

, et al. SIV-associated myocarditis: viral and cellular correlates of inflammation severity. AIDS Res Hum Retroviruses. 2006;22(6):529–540.

52.

Zhang

Wang

, et al. First molecular characterization of feline immunodeficiency virus in domestic cats from Mainland China. PLoS ONE. 2017;12(1):e0169739.

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