Our findings imply that HAD patients exhibited impaired serological responses that may lead to the emergence of viral mutants that potentially could infect the brain and mediate neurodegeneration.

No abstract

SummaryIn Pseudomonas aeruginosa, synthesis of pilin, the major protein subunit of the pili, is regulated by a two-component signal transduction system in which PilS is the sensor kinase. PilS is an inner membrane protein found at the poles of the bacterial cell. It is composed of three domains: an N-terminal hydrophobic domain; a central cytoplasmic linker region; and the C-terminal transmitter region conserved among other sensor kinases. The signal that activates PilS and, consequently, pilin transcription remains unknown. The membrane topology of the hydrophobic domain was determined using the lacZ and phoA gene fusion approach. In this report, we describe a topological model for PilS in which the hydrophobic domain forms six transmembrane helices, whereas the N-and C-termini are cytoplasmic. This topology is very stable, and the cytoplasmic C-terminus cannot cross the inner membrane. We also show that two of the six transmembrane segments are sufficient for membrane anchoring and polar localization of PilS.

Sindbis virus (SIN) expression vectors offer the opportunity for studying neuropathogenesis because of their distinct neural cell tropism. Here, we demonstrate that a recombinant SIN vector expressing EGFP (SINrep5-EGFP) infected multiple cell types including neural cells from several species relevant to lentivirus pathogenesis with high levels of transgene expression. Infection of human neurons by a recombinant SIN (SINrep5-JRFL) expressing the full-length envelope from a neurovirulent human immunodeficiency virus type 1 (HIV-1) strain (JRFL) caused increased cytotoxicity compared to infection with SINrep5-EGFP (P < 0.001), while no cytotoxicity was observed among infected human astrocytes or monocytoid cells. Both human monocyte-derived macrophages (MDM) (P < 0.01) and astrocytes (P < 0.001) infected with SINrep5-JRFL released soluble neurotoxins in contrast to SINrep5-EGFP or mock-infected cells, although this was most prominent for the astrocytes. Implantation of SINrep5-JRFL into the brains of SCID/NOD mice induced neuroinflammation, neuronal loss, and neurobehavioral changes characteristic of HIV-1 infection, which were not present in SINrep5-EGFP or mock-infected animals. Thus SIN expression vectors represent novel tools for studying in vitro and in vivo HIV-1 neuropathogenesis because of their high levels of transgene expression in specific cell types within the brain.

New treatment guidelines for acute rhinosinusitis outline when antibiotic therapy is appropriate, as well as describe evidence-based treatment to relieve symptoms, prevent complications, and prevent chronic disease.