HIV in central nervous system and behavioral development

Kinman, Loren; Worlein, Julie M.; Leigh, Jennifer; Bielefeldt‐Ohmann, Helle; Anderson, David; Hu, Shiu Lok; Morton, William R.; Anderson, Bradley D.; Ho, Rodney J. Y.

doi:10.1097/01.aids.0000131307.62828.a1

Cited by 11 publications

(13 citation statements)

References 33 publications

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“…Likewise, in the several models of pediatric SIV infection, subjects have shown cognitive and motor delays, 129 elevated CSF markers of neuronal death, periventricular white matter loss, microgliosis, 130 perivascular lymphocyte infiltration, 106,130 hippocampal neuronal loss, immature neuronal loss, and demyelination. 155 Results from both rodent and nonhuman primate models support face validity based on similar behavioral/cognitive signs and biological markers to those reported in HIV-1 infected children. 124 …”

Section: Animal Model Systemssupporting

confidence: 54%

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

Carryl¹,

Swang²,

Lawrence³

et al. 2015

ACS Chem. Neurosci.

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Pediatric human immunodeficiency virus (HIV-1) infection remains a global health crisis. Children are much more susceptible to HIV-1 neurological impairments than adults, which can be exacerbated by coinfections. Neurological characteristics of pediatric HIV-1 infection suggest dysfunction in the frontal cortex as well as the hippocampus; limited MRI data indicate global cerebral atrophy, and pathological data suggest accelerated neuronal apoptosis in the cortex. An obstacle to pediatric HIV-1 research is a human representative model system. Host-species specificity of HIV-1 limits the ability to model neurological consequences of pediatric HIV-1 infection in animals. Several models have been proposed including neonatal intracranial injections of HIV-1 viral proteins in rats and perinatal simian immunodeficiency virus (SIV) infection of infant macaques. Nonhuman primate models recapitulate the complexity of pediatric HIV-1, neuropathogenesis while rodent models are able to elucidate the role specific viral proteins exert on neurodevelopment. Nonhuman primate models show similar behavioral and neuropathological characteristics to pediatric HIV-1 infection and offer a stage to investigate early viral mechanisms, latency reservoirs, and therapeutic interventions. Here we review the relative strengths and limitations of pediatric HIV-1 model systems.

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Section: Animal Model Systemssupporting

confidence: 54%

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

Carryl¹,

Swang²,

Lawrence³

et al. 2015

ACS Chem. Neurosci.

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“…Detection of viral RNA in CSF paralleled a rise in QUIN levels in juvenile macaques infected with HIV-2287 (Kinman et al, 2004).…”

Section: Increased Quin Within the Csf And Brain Tissuementioning

confidence: 94%

Involvement of quinolinic acid in aids dementia complex

2005

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Human immunodeficiency virus (HIV) infection is often complicated by the development of acquired immunodeficiency syndrome (AIDS) dementia complex (ADC). Quinolinic acid (QUIN) is an end product of tryptophan, metabolized through the kynurenine pathway (KP) that can act as an endogenous brain excitotoxin when produced and released by activated macrophages/microglia, the very cells that are prominent in the pathogenesis of ADC. This review examines QUIN's involvement in the features of ADC and its role in pathogenesis. We then synthesize these findings into a hypothetical model for the role played by QUIN in ADC, and discuss the implications of this model for ADC and other inflammatory brain diseases.

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“…Despite the importance of neuropathological outcomes of intrauterine virus infections in humans (Dommergues et al. 1996; Volpe 2008), there are few appropriate models other than non‐human primate models, which are costly and inherently fraught with ethical problems (Kinman et al. 2004; Jayaraman et al.…”

mentioning

confidence: 99%

Neuro‐invasion by a ‘Trojan Horse’ strategy and vasculopathy during intrauterine flavivirus infection

Bielefeldt‐Ohmann

Смирнова

Tolnay

et al. 2012

Int J Experimental Path

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The central nervous system (CNS) is a major target of several important human and animal viral pathogens causing congenital infections. However, despite the importance of neuropathological outcomes, for humans in particular, the pathogenesis, including mode of neuro-invasion, remains unresolved for most congenital virus infections. Using a natural model of congenital infection with an RNA virus, bovine viral diarrhoea virus in pregnant cattle, we sought to delineate the timing and mode of virus neuro-invasion of and spread within the brain of foetuses following experimental respiratory tract infection of the dams at day 75 of pregnancy, a time of maximal risk of tissue pathology without foetal death. Virus antigen was first detected in the foetal brains 14 days postinfection of dams and was initially restricted to amoeboid microglial cells in the periventricular germinal layer. The appearance of these cells was preceded by or concurrent with vasculopathy in the same region. While the affected microvessels were negative for virus antigen, they expressed high levels of the type I interferon-stimulated protein ISG15 and eventually disappeared in parallel with the appearance of microcavitary lesions. Subsequently, the virus spread to neurons and other glial cells. Our findings suggest that the virus enters the CNS via infected microglial precursors, the amoeboid microglial cells, in a 'Trojan horse' mode of invasion and that the microcavitary lesions are associated with loss of periventricular microvasculature, perhaps as a consequence of high, unrestricted induction of interferon-regulated proteins.

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HIV in central nervous system and behavioral development

Cited by 11 publications

References 33 publications

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

Involvement of quinolinic acid in aids dementia complex

Neuro‐invasion by a ‘Trojan Horse’ strategy and vasculopathy during intrauterine flavivirus infection

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