Applications of the FIV Model to Study HIV Pathogenesis

Abstract

Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and the mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data that highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked, resource for advancing therapies and the management of HIV/AIDS.

Molecular detection ofPneumocystisin the lungs of cats

“…Along similar lines, FIV is a very well-studied lentivirus of cats, and despite great scrutiny in both experimental and naturally occurring settings, no association has ever been made between development of PCP and long-standing FIV infection in cats with greatly reduced numbers of circulating CD4 cells. 14 Results of the present study support the notion that cats can be asymptomatically infected by Pneumocystis spp. Such cats are likely to be colonized or subclinically infected but not in association with substantial tissue destruction or injury, and thus with no discernible lung dysfunction.…”

“…13 Perhaps more surprisingly, the same is true of the feline immunodeficiency virus (FIV). 14 Spontaneous PCP in cats has not been reported. Cats receiving renal transplants, for example, have never developed PCP despite being susceptible to numerous other opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans/ Cryptococcus gattii because of prednisone and cyclosporine administration.…”

Investigation of the Pentathiepin Functionality as an Inhibitor of Feline Immunodeficiency Virus (FIV) via a Potential Zinc Ejection Mechanism, as a Model for HIV Infection

“…During the course of our investigations we also demonstrated the validity of the FIV model for use as a HIV‐1 surrogate with 53 % sequence similarity in the minimized model (Figure ), which is supported by a number of recent reviews …”

“…[72] During the course of our investigations we also demonstrated the validity of the FIV model for use as aH IV-1 surrogate with 53 %s equence similarity in the minimizedm odel ChemMedChem 2019, 14,454 -461 www.chemmedchem.org (Figure 9), which is supported by an umber of recentr eviews. [73][74][75] The sub-micromolar potencies of these compounds coupled with moderate toxicities show an interesting avenue of investigation toward the development of ac andidate compound for targetingt he FIV/HIV NCp. The low toxicitya nd good activity of the initial thiopheneh it 14 that precipitated our initial investigation was improved by substitution with an alkyl pyrrole scaffold.H owever,t he simple trimethyl-substituted compound 20 a was highly active, albeit with some toxicity.C ompound 20 c was the most interesting result with slightly lower activity but significantly decreased toxicity.T his suggestst hat there is potentialt or educe any nonspecific toxicity associatedw ith this scaffold, and it is not the pentathiepin functionality itself that is the toxic motif,r ather the electronic contributions from the pendant arms.…”

Variation in Intra-individual Lentiviral Evolution Rates: a Systematic Review of Human, Nonhuman Primate, and Felid Species

“…A considerable body of research documents evolution rates of human immunodeficiency virus (HIV) and its analogues, simian immunodeficiency virus (SIV) and feline immunodeficiency virus (FIV). Shared similarities in lymphoid tropism, disease chronicity, and immunodeficiency outcomes support the use of SIV and FIV as evolutionary models for HIV/AIDS studies (7)(8)(9)(10). It is accepted that HIV type 1 (HIV-1) arose in humans following contacts with nonhuman primates and epidemic HIV-1 resulted after human adaptation (11).…”