The Comparative Value of Feline Virology Research: Can Findings from the Feline Lentiviral Vaccine Be Translated to Humans?

Hosie, Margaret J.; Techakriengkrai, Navapon; Bęczkowski, Paweł M.; Harris, Matthew N.; Logan, Nicola; Willett, Brian J.

doi:10.3390/vetsci4010007

Cited by 6 publications

(7 citation statements)

References 62 publications

(88 reference statements)

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“…The domestic cat is an attractive model for studying viral pathology and immunology in humans, especially for researching AIDS. The interaction of FIV with its primary receptor changes during the disease development, which is parallel to the way HIV switches its receptor as AIDS progresses (41). FIV is the only lentivirus for which a commercial vaccine is available for prevention in either human or veterinary medicine.…”

Section: Discussionmentioning

confidence: 99%

Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides

Liang

Sun

Liu

et al. 2018

J Virol

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Feline immunodeficiency virus (FIV) infection in domestic cats is the smallest usable natural model for lentiviral infection studies. FLA-E*01801 was applied to FIV AIDS vaccine research. We determined the crystal structure of FLA-E*01801 complexed with a peptide derived from FIV (gag positions 40 to 48; RMANVSTGR [RMA9]). The A pocket of the FLA-E*01801 complex plays a valuable restrictive role in peptide binding. Mutation experiments and circular-dichroism (CD) spectroscopy revealed that peptides with Asp at the first position (P1) could not bind to FLA-E*01801. The crystal structure and refolding of the mutant FLA-E*01801 complex demonstrated that Glu and Trp in the A pocket play important roles in restricting P1D. The B pocket of the FLA-E*01801 complex accommodates M/T/A/V/I/L/S residues, whereas the negatively charged F pocket prefers R/K residues. Based on the peptide binding motif, 125 FLA-E*01801-restricted FIV nonapeptides (San Diego isolate) were identified. Our results provide the structural basis for peptide presentation by the FLA-E*01801 molecule, especially A pocket restriction on peptide binding, and identify the potential cytotoxic T lymphocyte (CTL) epitope peptides of FIV presented by FLA-E*01801. These results will benefit both the reasonable design of FLA-E*01801-restricted CTL epitopes and the further development of the AIDS vaccine. Feline immunodeficiency virus (FIV) is a viral pathogen in cats, and this infection is the smallest usable natural model for lentivirus infection studies. To examine how FLA I presents FIV epitope peptides, we crystallized and solved the first classic feline major histocompatibility complex class I (MHC-I) molecular structure. Surprisingly, pocket A restricts peptide binding. Trp blocks the left side of pocket A, causing P1D to conflict with Glu We also identified the FLA-E*01801 binding motif X (except D)-(M/T/A/V/I/L/S)-X-X-X-X-X-X-(R/K) based on structural and biochemical experiments. We identified 125 FLA-E*01801-restricted nonapeptides from FIV. These results are valuable for developing peptide-based FIV and human immunodeficiency virus (HIV) vaccines and for studying how MHC-I molecules present peptides.

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Section: Discussionmentioning

confidence: 99%

Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides

Liang

Sun

Liu

et al. 2018

J Virol

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“…It has been shown that FIV is an effective model for studying HIV, in hopes that any vaccines developed for FIV can be extended to HIV. Therefore, it is critical to properly address the welfare needs of these models [ 34 ]. Long-term confinement, common in laboratory cats, is a welfare concern for animals, and enrichment is an integral component of their welfare.…”

Section: Discussionmentioning

confidence: 99%

Enrichment Preferences of FIV-Infected and Uninfected Laboratory-Housed Cats

Kennedy

Thomson²,

Griffith

et al. 2018

Viruses

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Environmental enrichment is critical for alleviating stress in laboratory felines. However, there is a paucity of information about suitable enrichment for cats. This study aimed to determine preferred enrichment options of individually-housed, castrated male domestic short hair cats (Felis catus) used in a longitudinal study of the effects of chronic feline immunodeficiency virus (FIV) infection, and to determine if the FIV status of the cats affected enrichment preferences. Preference testing was performed with two types of grooming brushes, three different interactive play options, including a laser, ball, and petting interaction with a familiar investigator, and two types of toenail conditioning objects. We found that cats elected to be brushed, preferred social interaction and play with the laser to the ball, and preferred to scratch on an inclined-box toenail conditioning object compared to a horizontal, circular toenail conditioning object. There were individual preferences for enrichment opportunities. There were no differences in preferences between FIV-infected and sham-infected cats. These enrichment preferences may be used to advise laboratory animal facilities and researchers about how to best accommodate the behavioral needs of laboratory cats.

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“…Moreover, some 4-amino-3,6-disulphonato-l,8-naphthalimide derivatives, such as dextran sulphate, pradimicin A, heparin, phosphonoformate, 2′3′-dideoxythymidine, 2′3′-dideoxyadenosine, and 2′3′-dideoxyinosine, have also been shown to have in vitro activity against FIV in various assays [ 6 ]. However, to date, no efficient drug or vaccine for FIV infection has been brought to the market [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Looking for Novel Capsid Protein Multimerization Inhibitors of Feline Immunodeficiency Virus

et al. 2018

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Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses. It causes acquired immunodeficiency syndrome (AIDS) in worldwide domestic and non-domestic cats and is a cause of an important veterinary issue. The genome organization of FIV and the clinical characteristics of the disease caused by FIV are similar to human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes, and macrophages, with a similar replication cycle in infected cells. Thus, the infection of cats with FIV is also a useful tool for the study and development of novel drugs and vaccines against HIV. Anti-retroviral drugs studied extensively with regards to HIV infection have targeted different steps of the virus replication cycle: (1) disruption of the interaction with host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus and cell membranes; (3) blocking of the reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and integration of viral DNA into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite the great success of anti-retroviral therapy in slowing HIV progression in humans, a similar therapy has not been thoroughly investigated for FIV infection in cats, mostly because of the little structural information available for FIV proteins. The FIV capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. During this step, the CA protein oligomerizes to form a protective coat that surrounds the viral genome. In this work, we perform a large-scale screening of four hundred molecules from our in-house library using an in vitro assembly assay of p24, combined with microscale thermophoresis, to estimate binding affinity. This screening led to the discovery of around four novel hits that inhibited capsid assembly in vitro. These may provide new antiviral drugs against FIV.

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The Comparative Value of Feline Virology Research: Can Findings from the Feline Lentiviral Vaccine Be Translated to Humans?

Cited by 6 publications

References 62 publications

Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides

Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides

Enrichment Preferences of FIV-Infected and Uninfected Laboratory-Housed Cats

Looking for Novel Capsid Protein Multimerization Inhibitors of Feline Immunodeficiency Virus

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