Miller Craig, Powers Jordan, Musselman Esther, Mackie Ryan, Elder John, VandeWoude Sue
Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, OK 74078, USA.
Department of Microbiology, Immunology, Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Viruses. 2019 Aug 30;11(9):805. doi: 10.3390/v11090805.
Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding immunomodulatory effects on FIV replication and persistence is critical to guide safe and effective therapies. To determine the immunologic and virologic effects of prednisolone and CsA during FIV infection, FIV-positive cats were administered immunosuppressive doses of prednisolone (2 mg/kg) or CsA (5 mg/kg). Both prednisolone and CsA induced acute and transient increases in FIV DNA and RNA loads as detected by quantitative PCR. Changes in the proportion of lymphocyte immunophenotypes were also observed between FIV-infected and naïve cats treated with CsA and prednisolone, and both treatments caused acute increases in CD4+ lymphocytes that correlated with increased FIV RNA. CsA and prednisolone also produced alterations in cytokine expression that favored a shift toward a Th2 response. Pre-treatment with CsA slightly enhanced the efficacy of antiretroviral therapy but did not enhance clearance of FIV. Results highlight the potential for drug-induced perturbation of FIV infection and underscore the need for more information regarding immunopathologic consequences of therapeutic agents on concurrent viral infections.
猫免疫缺陷病毒（FIV）可在慢性感染的猫中引发机会性疾病，泼尼松龙和环孢素A（CsA）在临床上都用于治疗淋巴瘤和口腔炎等并发症。然而，这些化合物对FIV感染的影响仍不清楚，了解其对FIV复制和持续存在的免疫调节作用对于指导安全有效的治疗至关重要。为了确定泼尼松龙和CsA在FIV感染期间的免疫和病毒学效应，对FIV阳性猫给予免疫抑制剂量的泼尼松龙（2mg/kg）或CsA（5mg/kg）。通过定量PCR检测发现，泼尼松龙和CsA均诱导FIV DNA和RNA载量急性和短暂增加。在用CsA和泼尼松龙治疗的FIV感染猫和未感染猫之间，还观察到淋巴细胞免疫表型比例的变化，两种治疗均导致CD4+淋巴细胞急性增加，这与FIV RNA增加相关。CsA和泼尼松龙还导致细胞因子表达改变，有利于向Th2反应转变。CsA预处理略微增强了抗逆转录病毒疗法的疗效，但并未增强FIV的清除率。结果突出了药物诱导FIV感染扰动的可能性，并强调需要更多关于治疗药物对并发病毒感染免疫病理后果的信息。
