This is a brief summary of the animal models session held during the 12th Annual Meeting of the Society on NeuroImmune Pharmacology, Santa Fe, NM, USA. This session provided important information for participants on availability and utility of animal models for the studies of HIV-1 central nervous system infection and drug abuse. It highlighted animal model relevance to human disease/condition, its utility for the studies of pathogenesis, potential importance for the development of therapeutics, and demonstrated limitations/pitfalls. (+info)
CD4 T cells contribute to virus control and pathology following central nervous system infection with neurotropic mouse hepatitis virus.
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Replication of the neurotropic mouse hepatitis virus strain JHM (JHMV) is controlled primarily by CD8(+) T-cell effectors utilizing gamma interferon (IFN-gamma) and perforin-mediated cytotoxicity. CD4(+) T cells provide an auxiliary function(s) for CD8(+) T-cell survival; however, their direct contribution to control of virus replication and pathology is unclear. To examine a direct role of CD4(+) T cells in viral clearance and pathology, pathogenesis was compared in mice deficient in both perforin and IFN-gamma that were selectively reconstituted for these functions via transfer of virus-specific memory CD4(+) T cells. CD4(+) T cells from immunized wild-type, perforin-deficient, and IFN-gamma-deficient donors all initially reduced virus replication. However, prolonged viral control by IFN-gamma-competent donors suggested that IFN-gamma is important for sustained virus control. Local release of IFN-gamma was evident by up-regulation of class II molecules on microglia in recipients of IFN-gamma producing CD4(+) T cells. CD4(+) T-cell-mediated antiviral activity correlated with diminished clinical symptoms, pathology, and demyelination. Both wild-type donor CD90.1 and recipient CD90.2 CD4(+) T cells trafficked into the central nervous system (CNS) parenchyma and localized to infected white matter, correlating with decreased numbers of virus-infected oligodendrocytes in the CNS. These data support a direct, if limited, antiviral role for CD4(+) T cells early during acute JHMV encephalomyelitis. Although the antiviral effector mechanism is initially independent of IFN-gamma secretion, sustained control of CNS virus replication by CD4(+) T cells requires IFN-gamma. (+info)
Highlights of the 15th Conference on Retroviruses and Opportunistic Infections. Neurologic complications of HIV disease and their treatment.
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New data were presented at the 15th Conference on Retroviruses and Opportunistic Infections that further support the importance of considering the neuroeffectiveness of antiretroviral drugs when designing treatment regimens. Two studies linked antiretroviral therapy that had estimates of better neuroeffectiveness with better global neuropsychologic outcomes in life. A third study linked estimates of better antiretroviral therapy neuroeffectiveness, particularly nonnucleoside analogue reverse transcriptase inhibitors, with a lower prevalence of HIV-associated brain pathology at death. Additional findings presented at the conference focused on the correlates of HIV-associated neurocognitive disorders (HAND) and peripheral neuropathy. Supporting the concept that viral factors influence the pathogenesis of HAND, high frequencies of HAND were identified in people infected with HIV subtype D and in people infected with subtype B and having brain-specific mutations in V3 of gp160. Supporting the importance of host correlates of HAND, important data from a macaque study identified a strong link between a major histocompatibility complex class I allele, Mane-A*10, and simian immunodeficiency virus encephalitis. Supporting the importance of comorbidities in determining risk for HAND, high levels of lipopolysaccharide in blood, likely derived from the HIV-injured intestine and bacterial translocation, were linked to HAND. Coinfections with JC virus or Treponema pallidum were topics of other presentations, identifying a prognostic marker for PML (better CD8+ cytotoxic T-lymphocyte responses were associated with survival) and a diagnostic one for neurosyphilis (CXCL13 levels in CSF). (+info)
Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: a mediator between peripheral infection and neurodegeneration?
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Epidemiology of neuroinvasive arboviral disease in the United States, 1999-2007.
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From 1999-2007, the most common causes of neuroinvasive arboviral disease in the United States, after West Nile virus (WNV), were California (CAL) serogroup viruses, St. Louis encephalitis virus (SLEV), and eastern equine encephalitis virus (EEEV). The CAL serogroup virus disease was primarily reported from Appalachia and the upper Midwest, SLEV disease from southern states, and EEEV disease from areas along the Atlantic and Gulf coasts. Children accounted for 88% of CAL serogroup virus disease, whereas 75% of SLEV disease occurred among older adults. The EEEV disease had the highest case-fatality rate (42%). The incidence of CAL serogroup virus and EEEV disease remained stable before and after the detection of WNV in the United States in 1999. The SLEV disease declined 3-fold after 1999; however, SLEV disease has occurred in sporadic epidemics that make trends difficult to interpret. The CAL serogroup virus, SLEV, and EEEV disease are persistent public health concerns in the United States warranting ongoing prevention efforts. (+info)
Cryptococcus gattii with bimorphic colony types in a dog in western Oregon: additional evidence for expansion of the Vancouver Island outbreak.
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Cryptococcus gattii was isolated from a 1.5-year-old dog with systemic cryptococcosis in Oregon. The dog had no link to Vancouver Island or British Columbia, Canada. Samples from a nasal swab and from a granulomatous mass within the cranial cavity were pooled for culture. Colonies on Sabouraud dextrose agar were mucoid and exhibited bimorphic morphology, melanin-pigmented and unpigmented. Pigmented colonies were encapsulated budding spherical yeast, whereas unpigmented colonies were of unencapsulated ovoid budding yeast. In addition to defective melanin production, the unpigmented colony type exhibited defective mating. Genetic analysis by high-resolution multilocus sequence typing revealed that the 2 isolates are genetically identical at 8 unlinked loci tested and that the 2 isolates are both the VGIIa Vancouver Island major genotype. Findings are consistent with expansion of the Vancouver Island outbreak onto the mainland Pacific Northwest region of the United States. (+info)