Pharmacological Inhibition of Feline Immunodeficiency Virus (FIV)

Abstract

Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

Efficacy of antiviral chemotherapy for retrovirus-infected cats

“…Many of these analogues are also integrated into elonga ting DNA or RNA strands, but because of small differences in molecular structure, this leads to chain termination or non-functional nucleic acids. 12,16,17 Nucleoside analogues are accepted as false substrates not only by viral enzymes, but also by cellular enzymes, which largely accounts for their toxicity.…”

“…15 They are classified as non-competitive inhibitors of RT and do not require intracellular activation to inhibit the enzyme. 15,16 Non-nucleoside RT inhibitors are a group of structurally diverse compounds that all bind a single site in the HIV RT enzyme. 72 The interaction with the allosteric site, which is located in close proximity to the catalytic site, leads to a number of conformational changes within the RT.…”

Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells

“…Most commonly, two of these drugs are NRTIs or a NRTI together with a nucleotide reverse transcriptase inhibitor (NtRTI) combined with a third agent from a different drug class (CIHLAR and RAY, 2010;TRESSLER and GODFREY, 2012). Despite this great success in human medicine, no such therapy is available for cats (ZEINALIPOUR-LOIZIDOU et al, 2007;PALMISANO and VELLA, 2011;MOHAMMADI and BIENZLE, 2012).…”

Feline Immunodeficiency

“…AZT (3'-azido-2',3'-dideoxythymidine) is a nucleoside analogue (thymidine derivative) that blocks the retroviral reverse transcriptase and inhibits the replication of FIV in vivo and in vitro. As with HIV, FIV resistance may arise after 6 months of treatment Doménech et al, 2011;Mohammadi & Bienzle, 2012).…”

“…The recombinant human erythropoietin is also used successfully in cats with non-regenerative anemia, administration elevates blood cells, without increasing the viral load. Treatment with insulin-like growth factor-1 recombinant human induces thymic growth and stimulates T cell function, resulting in a significant increase in thymus size and thymic cortical regeneration, replenishing the peripheral T cell pool in experimentally FIVinfected cats Mohammadi & Bienzle, 2012).…”