Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence

Abstract

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.

Fatal disseminated toxoplasmosis in a feline immunodeficiency virus‐positive cat receiving oclacitinib for feline atopic skin syndrome

“…Retroviral infections including FIV and human immunodeficiency virus (HIV) cause CD4+ T‐lymphocyte cytopaenia and dysfunction 4,5 . HIV is a risk factor for toxoplasmosis in humans due to immunosuppression.…”

“…HIV is a risk factor for toxoplasmosis in humans due to immunosuppression. Likewise, FIV‐positive cats are predisposed to toxoplasmosis and other opportunistic infections, especially when receiving immunosuppressive drugs 4 . Recently, JAK inhibitors have been described to exhibit anti‐viral activity through their ability to decrease the multiplication of virally infected cells in people with HIV, thereby inhibiting HIV latency reactivation through T‐lymphocyte suppression 9 .…”

“…Systemic toxoplasmosis has been reported in immunocompetent adult cats, cats receiving cyclosporin or prednisolone for FASS 3,4 and immunocompromised cats with feline immunodeficiency virus (FIV) or feline leukaemia virus 5 . The risks of using oclacitinib in immunosuppressed cats has not been evaluated.…”

SARS CoV-2 (Delta Variant) Infection Kinetics and Immunopathogenesis in Domestic Cats

“…RNA was extracted from tissue homogenates using Qiagen RNeasy Mini kit (Qiagen, Germantown, MD, USA) according to the manufacturer's recommendations and as previously described [26]. RNA from each sample was converted to cDNA using Superscript II reverse transcriptase (Invitrogen, Carlsbad, CA, USA) in individual reactions with random hexamers (Invitrogen) and treated with RNase Out (Invitrogen) prior to droplet digital PCR quantification as previously described [47]. Droplet Digital PCR [48] was performed to quantify SARS-CoV-2 viral loads using N1 and N2 primers (500 nM each) and probe (at 250) (Caltalog#10006713, Integrated DNA Technologies, Inc., Coralville, Iowa).…”

Advances in Feline Viruses and Viral Diseases

“…Use of prednisolone and cyclosporine A (CsA) is sometimes indicated in FIV-infected cats to treat secondary diseases, such as immune-mediated disease, stomatitis, or lymphoma, but the effects of these drugs on FIV replication and persistence are poorly understood. Miller et al investigated the immunomodulatory effects of prednisolone and CsA in cats with FIV infection, reporting acute, transient increases in FIV DNA and RNA and CD4+ lymphocytes, as well as cytokine expression, which favored a shift toward a Th2 response [ 21 ].…”