Neurobehavioral Performance in Feline Immunodeficiency Virus Infection: Integrated Analysis of Viral Burden, Neuroinflammation, and Neuronal Injury in Cortex

Maingat, Ferdinand; Vivithanaporn, Pornpun; Zhu, Yu; Taylor, Andrew J.; Baker, Glen B.; Pearson, K. G.; Power, Christopher

doi:10.1523/jneurosci.5818-08.2009

Cited by 30 publications

(36 citation statements)

References 38 publications

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“…Breeding pairs were negative for feline retroviruses (FIV, Feline Leukemia Virus; FeLV) by PCR analysis and serologic testing. Animals were injected intracranially (right frontal lobe) one day post-partum with 200 µl of virus (10 4 TCID 50 /ml) [44]. Animals were weaned after 6 weeks and monitored over 12 weeks post-infection during which time body weight was measured, neurobehavioral tests performed and blood samples collected.…”

Section: Methodsmentioning

confidence: 99%

Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status

et al. 2013

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The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity. To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/AIDS [HIV] (n = 12), other disease controls [ODC] (n = 14) and in cerebral surgical resections for epilepsy [SURG] (n = 6). Deep sequencing of cerebral white matter-derived RNA from the HIV (n = 4) and ODC (n = 4) patients and SURG (n = 2) groups revealed bacterially-encoded 16 s RNA sequences in all brain specimens with α-proteobacteria representing over 70% of bacterial sequences while the other 30% of bacterial classes varied widely. Bacterial rRNA was detected in white matter glial cells by in situ hybridization and peptidoglycan immunoreactivity was also localized principally in glia in human brains. Analyses of amplified bacterial 16 s rRNA sequences disclosed that Proteobacteria was the principal bacterial phylum in all human brain samples with similar bacterial rRNA quantities in HIV and ODC groups despite increased host neuroimmune responses in the HIV group. Exogenous viruses including bacteriophage and human herpes viruses-4, -5 and -6 were detected variably in autopsied brains from both clinical groups. Brains from SIV- and SHIV-infected macaques displayed a profile of bacterial phyla also dominated by Proteobacteria but bacterial sequences were not detected in experimentally FIV-infected cat or RAG1−/− mouse brains. Intracerebral implantation of human brain homogenates into RAG1−/− mice revealed a preponderance of α-proteobacteria 16 s RNA sequences in the brains of recipient mice at 7 weeks post-implantation, which was abrogated by prior heat-treatment of the brain homogenate. Thus, α-proteobacteria represented the major bacterial component of the primate brain’s microbiome regardless of underlying immune status, which could be transferred into naïve hosts leading to microbial persistence in the brain.

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Section: Methodsmentioning

confidence: 99%

Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status

et al. 2013

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“…Viral load is a key marker of in vivo viral burden, and its measurement in blood is a useful indicator of systemic disease status (38,39). Animals that were repeatedly exposed to LPS showed signs of sickness behavior for ∼1-2 h after injection, as evidenced by reduced motor activity, sleep, and ruffled coat, but promptly recovered in all cases.…”

Section: Systemic Lps Exposure Reduced Viral Burdenmentioning

confidence: 99%

Regulation of Lentivirus Neurovirulence by Lipopolysaccharide Conditioning: Suppression of CXCL10 in the Brain by IL-10

Maingat

Viappiani

Zhu

et al. 2009

The Journal of Immunology

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Lentivirus infections including HIV and feline immunodeficiency virus (FIV) cause neurovirulence, which is largely mediated by innate immunity. To investigate the interactions between neurovirulence and repeated conditioning by innate immune activation, models of lentivirus infection were exposed to LPS. Gene expression in HIV-infected (HIV+) and control (HIV−) patient brains was compared by real time RT-PCR and immunocytochemistry. Supernatants from mock and HIV-infected monocyte-derived macrophages exposed to LPS were applied to human neurons. FIV-infected (FIV+) and control (FIV−) animals were exposed repeatedly to LPS postinfection together with concurrent neurobehavioral testing, viral load, and host gene analyses. Brains from HIV+ individuals exhibited induction of CD3ε, CXCL10, and granzyme A expression (p < 0.05). Supernatants from HIV+ monocyte-derived macrophages induced CXCL10 expression in neurons, which was diminished by IL-10 treatment (p < 0.05). LPS-exposed FIV+ animals demonstrated lower plasma and brain viral loads (p < 0.05). Neuronal CXCL10 expression was increased in FIV+ animals but was suppressed by LPS exposure, together with reduced brain CD3ε and granzyme A expression (p < 0.05). In conjunction with preserved NeuN-positive neuronal counts in parietal cortex (p < 0.05), FIV+ animals exposed to LPS also showed less severe neurobehavioral deficits (p < 0.05). Repeated LPS exposures suppressed CXCL10 in the brain and ensuing T cell infiltration with a concomitant reduction in neurovirulence. Thus, innate immune chronic conditioning exerted beneficial effects on neurovirulence through suppression of a specific chemotactic factor, CXCL10, mediated by IL-10, leading to reduced leukocyte infiltration and release of neurotoxic factors.

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“…More recent tests have employed increasingly sensitive measures of cognitive and motor function in FIV infected cats. Increases in gait width, greater errors in a stepping task and increased maze completion times in a modified T-maze were found to correlate with inflammatory markers and CNS FIV viral burden (Malingat et al, 2009). These studies reveal the potential of behavioral studies to assess neural function in cats but also highlight the need for more sensitive and standardized approaches.…”

Section: Introductionmentioning

confidence: 99%

The use of a T-maze to measure cognitive–motor function in cats (Felis catus)

Sherman

Gruen

Meeker

et al. 2013

Journal of Veterinary Behavior

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Few tests have been developed to test the cognitive and motor capabilities of domestic cats, in spite of the suitability of cats for specific studies of neuroanatomy, infectious diseases, development, aging, and behavior. The present study evaluated a T-maze apparatus as a sensitive and reliable measure of cognition and motor function of cats. Eighteen purpose-bred, specific-pathogen-free, male, neutered domestic shorthair cats (Felis catus), 1-2 years of age, were trained and tested to a T-maze protocol using food rewards. The test protocol consisted of positional discrimination training (left arm or right arm) to criterion followed by two discrimination reversal tests. The two reversal tests documented the ability of the subjects to respond to a new reward location, and switch arms of the T-maze. Data were collected on side preference, number of correct responses, and latency of responses by the subjects. Aided by a customized computer program (CanCog Technologies), data were recorded electronically as each cat progressed from the start box to the reward arm. The protocol facilitated rapid training to a high and consistent level of performance during the discrimination training. This learning was associated with a decrease in the latency to traverse the maze to a mean of 4.80 ± 0.87 s indicating strong motivation and consistent performance. When the rewarded side was reversed in the test phase, cats required more trials to reach criterion, as expected, but again showed reliable learning. The latency to reward in the first session of reversal increased 86% from the first to the last trial indicating that it may provide a useful index of cognitive processing. Latencies subsequently decreased as the new reversal paradigm was learned. This paradigm provides a relatively rapid and reliable test of cognitive motor performance that can be used in various settings for evaluation of feline cognitive and motor function.

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Neurobehavioral Performance in Feline Immunodeficiency Virus Infection: Integrated Analysis of Viral Burden, Neuroinflammation, and Neuronal Injury in Cortex

Cited by 30 publications

References 38 publications

Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status

Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status

Regulation of Lentivirus Neurovirulence by Lipopolysaccharide Conditioning: Suppression of CXCL10 in the Brain by IL-10

The use of a T-maze to measure cognitive–motor function in cats (Felis catus)

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