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

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 <i>interferon-gamma</i>, <i>tumor necrosis factor-alpha</i>, <i>interleukin (IL)-17</i>, and <i>transforming growth factor-beta</i> than the controls, whereas the myocardium exhibited significantly higher <i>IL-17</i> and lower <i>IL-13</i> 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.