Feline immunodeficiency virus latency

McDonnel, Samantha J.; Sparger, Ellen E.; Murphy, Brian G

doi:10.1186/1742-4690-10-69

Cited by 14 publications

(22 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Table 1 summarizes key studies that have identified FIV cell reservoirs and the modalities used to detect infection or susceptibility to infection. It is important to note that the leukocyte subsets that have proven most consistently infected in vivo and susceptible to infection in vitro are CD4+ T cells and monocyte/ macrophages, which are also target cell reservoirs for HIV [13,49,54,[60][61][62]. Evidence thus far is conflicting regarding productive infection of dendritic cells in vivo [29,30,54,63], although multiple studies support productive FIV infection of cultivated dendritic cells [43,63,64].…”

Section: Cell Reservoirs Of Fivmentioning

confidence: 99%

“…Latently infected cells are thus of key importance when considering viral reservoirs, particularly within a host on ART. McDonnel et al reviewed FIV latency and the strengths of the FIV-infected cat as a model of the HIV-infected human [61]. Different cohorts of naturally and experimentally infected cats have demonstrated either undetectable or consistently detectable plasma viraemia during the asymptomatic phase, which may be due to differences in viral strains, inoculating dose, age of the animal or other factors [7,84,98,104,[115][116][117][118].…”

Section: Fiv Latencymentioning

confidence: 99%

See 1 more Smart Citation

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Eckstrand

Sparger

Murphy

2017

Journal of General Virology

View full text Add to dashboard Cite

Infection with feline immunodeficiency virus (FIV), a lentivirus similar to human immunodeficiency virus (HIV), results in lifelong viral persistence and progressive immunopathology in the cat. FIV has the ability to infect and produce infectious virus in a number of different cell types. FIV provirus can also be maintained in a replication-competent but transcriptionally quiescent state, facilitating viral persistence over time. Immediately after the initial infection, FIV infection quickly disseminates to many anatomical compartments within the host including lymphoid organs, gastrointestinal tract and brain. Collectively, the anatomic and cellular compartments that harbour FIV provirus constitute the viral reservoir and contain foci of both ongoing viral replication and transcriptionally restricted virus that may persist over time. The relative importance of the different phenotypes observed for infected cells, anatomic compartment, replication status and size of the reservoir represent crucial areas of investigation for developing effective viral suppression and eradication therapies. In this review, we discuss what is currently known about FIV reservoirs, and emphasize the utility of the FIV-infected cat as a model for the HIV-infected human.

show abstract

Section: Cell Reservoirs Of Fivmentioning

confidence: 99%

Section: Fiv Latencymentioning

confidence: 99%

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Eckstrand

Sparger

Murphy

2017

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Multiple molecular mechanisms may underlie the establishment and maintenance of latently-infected cellular reservoirs (Margolis, 2010), including epigenetic modification of histone proteins in chromatin (Colin and Van Lint, 2009; Imai et al, 2010; Margolis, 2010, 2011). FIV has been established as an outbred, large animal model of lentiviral latency, reviewed in (McDonnel et al, 2013). Studies in our laboratory demonstrated that domestic cats experimentally infected with FIV exhibit a state of latency in peripheral blood CD4+ T-cells with concurrent undetectable plasma viremia approximately 8 months after inoculation (Murphy et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Use of the FIV-infected cat model of lentiviral latency may help address questions that are either logistically or ethically not feasible in HIV-infected humans, including the investigation of histone-modifying agents and other novel therapeutic antilatency approaches (McDonnel et al, 2013). Importantly, these findings have the potential to benefit FIV-infected cats as well as HIV-infected humans.…”

Section: Introductionmentioning

confidence: 99%

Treatment of chronically FIV-infected cats with suberoylanilide hydroxamic acid

2014

View full text Add to dashboard Cite

Feline immunodeficiency virus (FIV) is a naturally-occurring, large animal model of lentiviral-induced immunodeficiency syndrome, and has been used as a model of HIV pathogenesis and therapeutic interventions. HIV reservoirs in the form of latent virus remain the primary roadblock to viral eradication and cure, and FIV has been previously established an animal model of lentiviral latency. The goal of this study was to determine whether administration of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) to aviremic, chronically FIV-infected cats would induce latent viral reactivation in vivo. A proof-of-concept experiment in a Transwell co-culture system demonstrated the ability of SAHA to reactivate latent virus which was replication competent and able to infect naïve cells. Oral SAHA (250 mg/m2) was administered with food to four asymptomatic, experimentally FIV-infected cats and one uninfected control cat, and a limited pharmacokinetic and pharmacodynamic analysis was performed. A statistically significant increase in cell-associated FIV RNA was detected in the cat with the greatest serum SAHA exposure, and cell-free viral RNA was detected at one time point in the three cats that achieved the highest levels of SAHA in serum. Interestingly, there was a significant decrease in viral DNA burden at 2 hours post drug administration in the same three cats. Though the sample size is small and the drug response was modest, this study provides evidence that in vivo treatment of FIV-infected cats with the HDACi SAHA can induce viral transcriptional reactivation, which may be dependent upon the concentration of SAHA achieved in blood. Importantly, alternative putative antilatency therapy drugs, and multimodal drug combinations, could be studied in this in vivo system. The FIV/cat model provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus in vivo.

show abstract

“…Quantification of plasma vRNA copy number was based on a standard curve previously described. [39] For assay of cell-associated vDNA and vRNA, real-time PCR assays of feline GAPDH were included in parallel using the same nucleic acid samples to normalize nucleic acid concentration as previously described. [11]…”

Section: Methodsmentioning

confidence: 99%

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

et al. 2017

View full text Add to dashboard Cite

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

show abstract

Feline immunodeficiency virus latency

Cited by 14 publications

References 113 publications

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Treatment of chronically FIV-infected cats with suberoylanilide hydroxamic acid

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

Contact Info

Product

Resources

About