Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status.

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.

Aicardi-Goutières syndrome: an important Mendelian mimic of congenital infection.

Aicardi-Goutières syndrome (AGS) is a rare, genetically determined encephalopathy whose importance from a clinical viewpoint is magnified because of the risk of misdiagnosis as the sequelae of congenital infection. Recent molecular advances have shown that AGS can be caused by mutations in any one of at least five genes (four of which have so far been identified), most commonly on a recessive basis but occasionally as a dominant trait. Additionally, a recent genotype-phenotype correlation has shown that two clinical presentations can be delineated; an early onset neonatal form highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Evidence is emerging to show that the nucleases defective in AGS are involved in removing endogenous nucleic acid species produced during normal cellular processing, and that a failure of this removal results in inappropriate activation of the innate immune system. This hypothesis explains the phenotypic overlap of AGS with congenital infection and some aspects of systemic lupus erythematosus, where a similar interferon alpha-mediated innate immune response is triggered by viral and host nucleic acids respectively.

Polymerase chain reaction in the diagnosis and management of central nervous system infections.

Polymerase chain reaction (PCR) is a broadly applied laboratory test for the diagnosis of a wide variety of central nervous system (CNS) diseases, including genetic and autoimmune diseases, malignant neoplasms, and infections. With its ability to detect minute amounts of DNA or RNA contained in tissues or fluids, PCR has improved the rapidity and accuracy of diagnosis, enhanced understanding of pathogenesis, and helped identify infectious causes for diseases previously considered idiopathic. In addition, PCR can be performed on a variety of tissues preserved in different ways--even archival specimens can be used to provide important epidemiological information. By making quick and precise diagnoses, appropriate treatments can be instituted, and unnecessary or invasive investigations can be avoided.