Utilizing the FIV model to understand dendritic cell dysfunction and the potential role of dendritic cell immunization in HIV infection

Lehman, Tracy L.; O’Halloran, Kevin P.; Hoover, Edward A.; Avery, P.

doi:10.1016/j.vetimm.2009.10.012

Cited by 9 publications

(7 citation statements)

References 79 publications

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“…45,48,49 Evidence also points to altered dendritic cell function during acute FIV infection. 50,51 The impairment of T-cell function in acute FIV infection has been suggested to result from cytokine dysregulation, immunologic anergy, and increased apoptosis. 45 In turn, this is associated with an inability to mount a primary immune response to opportunistic pathogens.…”

Section: Feline Immunodeficiency Virus Infectionmentioning

confidence: 99%

Immunodeficiencies Caused by Infectious Diseases

Sykes

2010

Veterinary Clinics of North America: Small Animal Practice

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Immunodeficiencies caused by infectious agents may result from disruption of normal host barriers or dysregulation of cellular immunity, the latter serving to promote survival of the infectious agent through immune evasion. Such infections may be followed by opportunistic infections with a variety of other microorganisms. Classic infectious causes of immunodeficiency in companion animals are the immunodeficiency retroviruses, including feline immunodeficiency virus and feline leukemia virus. Other important causes include canine distemper virus; canine parvovirus 2; feline infectious peritonitis virus; rickettsial organisms that infect leukocytes; Leishmania; and fungal pathogens, such as Cryptococcus. Considerable research effort has been invested in understanding the mechanisms of pathogen-induced immunosuppression, with the hope that effective therapies may be developed that reverse the immunodeficiencies developed and in turn assist the host to clear persistent or life-threatening infectious diseases.

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Section: Feline Immunodeficiency Virus Infectionmentioning

confidence: 99%

Immunodeficiencies Caused by Infectious Diseases

Sykes

2010

Veterinary Clinics of North America: Small Animal Practice

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“…However, highly pathogenic FIV isolates can cause mortality up to 60 % under experimental conditions [ 25 – 27 ]. Thus, FIV infection of cats is a valuable animal model to study HIV-1 and AIDS [ 28 – 30 ]. In addition to the domestic cat, species-specific FIVs that might cause disease in some natural hosts have been isolated in many Felidae [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Determinants of FIV and HIV Vif sensitivity of feline APOBEC3 restriction factors

Zhang

Vasudevan

et al. 2016

Retrovirology

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BackgroundFeline immunodeficiency virus (FIV) is a global pathogen of Felidae species and a model system for Human immunodeficiency virus (HIV)-induced AIDS. In felids such as the domestic cat (Felis catus), APOBEC3 (A3) genes encode for single-domain A3Z2s, A3Z3 and double-domain A3Z2Z3 anti-viral cytidine deaminases. The feline A3Z2Z3 is expressed following read-through transcription and alternative splicing, introducing a previously untranslated exon in frame, encoding a domain insertion called linker. Only A3Z3 and A3Z2Z3 inhibit Vif-deficient FIV. Feline A3s also are restriction factors for HIV and Simian immunodeficiency viruses (SIV). Surprisingly, HIV-2/SIV Vifs can counteract feline A3Z2Z3.ResultsTo identify residues in feline A3s that Vifs need for interaction and degradation, chimeric human–feline A3s were tested. Here we describe the molecular direct interaction of feline A3s with Vif proteins from cat FIV and present the first structural A3 model locating these interaction regions. In the Z3 domain we have identified residues involved in binding of FIV Vif, and their mutation blocked Vif-induced A3Z3 degradation. We further identified additional essential residues for FIV Vif interaction in the A3Z2 domain, allowing the generation of FIV Vif resistant A3Z2Z3. Mutated feline A3s also showed resistance to the Vif of a lion-specific FIV, indicating an evolutionary conserved Vif–A3 binding. Comparative modelling of feline A3Z2Z3 suggests that the residues interacting with FIV Vif have, unlike Vif-interacting residues in human A3s, a unique location at the domain interface of Z2 and Z3 and that the linker forms a homeobox-like domain protruding of the Z2Z3 core. HIV-2/SIV Vifs efficiently degrade feline A3Z2Z3 by possible targeting the linker stretch connecting both Z-domains.ConclusionsHere we identified in feline A3s residues important for binding of FIV Vif and a unique protein domain insertion (linker). To understand Vif evolution, a structural model of the feline A3 was developed. Our results show that HIV Vif binds human A3s differently than FIV Vif feline A3s. The linker insertion is suggested to form a homeo-box domain, which is unique to A3s of cats and related species, and not found in human and mouse A3s. Together, these findings indicate a specific and different A3 evolution in cats and human.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0274-9) contains supplementary material, which is available to authorized users.

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“…In most naturally infected domestic cats (Felis catus, Fca), FIV causes a severe immune deficiency only in a subpopulation of animals; however, highly pathogenic feline AIDS-inducing FIV isolates have been described (26)(27)(28)(29). Thus, FIV infections in cats are a relevant animal model for studying lentiviral AIDS induction and immune control leading to nonprogression (30)(31)(32)(33). It is known that the pandemic of HIV originated from cross-species transmission events of SIVs to hu-mans (34).…”

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confidence: 99%