No abstract

The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.The mechanisms involved in the development of central nervous system (CNS) lesions are readily understood only in those pathological conditions in which there is evidence that a virus destroys its target cell as a direct cytopathic consequence of viral replication (e.g., polio virus or other neurotrophic viruses; refs. 1 and 2). However, the effector mechanisms involved in tissue damage associated with a far wider variety of viral infections of the CNS, involving such viruses as the measles and rubella viruses as well as human immunodeficiency virus 1, are unclear. Likewise, the mediators responsible for the CNS damage associated with chronic neurologic diseases such as multiple sclerosis remain the subject of speculation. Interestingly, morphologic analyses have revealed that lesions in affected brain tissues are frequently surrounded by infiltrating inflammatory cell populations. Although the precise role that these cells play in CNS pathology is the subject of ongoing investigation, previous studies have focused on the ability of leukocyte populations to generate proinflammatory cytokines (e.g., interleukin 1, tumor necrosis factor, etc.), neurotoxins (e.g., quinolinic acid), or reactive oxygen intermediates (3). Recently, increased attention has focused on the possibility that reactive nitrogen intermediates (NOI) generated by a family of cytochrome P-450 reductase-like enzymes, the nitric oxide synthases (NOS), directly damage host tissues in a diverse array of pathogenic states (4).To date, at least three NOS genes have been cloned and characterized, and these have been provisionally categorized on the basis of their sensitivity to regulation by Ca2+ transients (4). In this schema, NOS forms that bind calmodulin in a reversible Ca2+-dependent manner are termed the constitutive forms of NOS, and those forms of the enzyme that bind calmodulin tightly at resting [Ca2+] are termed inducible NOSs (iNOSs). After the addition of rapid-acting agonists, the constitutive NOS system generates only low levels of the NOI, nitric oxide (NO), whereas the iNOS system begins to generate NO several hours after exposure to cyto...

This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.

Plant genetic engineering led to the production of plant-derived mAb (mAb P ), which provides a safe and economically feasible alternative to the current methods of antibody production in animal systems. In this study, the heavy and light chains of human anti-rabies mAb were expressed and assembled in planta under the control of two strong constitutive promoters. An alfalfa mosaic virus untranslated leader sequence and Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum retention signal were linked at the N and C terminus of the heavy chain, respectively. mAb P was as effective at neutralizing the activity of the rabies virus as the mammalianderived antibody (mAb M ) or human rabies Ig (HRIG). The mAb P contained mainly oligomannose type N-glycans (90%) and had no potentially antigenic ␣(1,3)-linked fucose residues. mAb P had a shorter half-life than mAb M . The mAb P was as efficient as HRIG for post-exposure prophylaxis against rabies virus in hamsters, indicating that differences in N-glycosylation do not affect the efficacy of the antibody in this model.