BAAV Transcytosis Requires an Interaction with β-1-4 Linked- Glucosamine and gp96

Cell surface carbohydrates play an important role in virus entry and intracellular trafficking. Bovine Adeno-Associated Virus (BAAV) uses plasma membrane gangliosides for transduction and infection. In addition, independent of the infectious pathway, BAAV also has the ability to pass through barrier epithelia and endothelia using a transcytosis pathway dependent upon the presence of cell surface carbohydrates. Thus, in order to better define the carbohydrate interactions that are necessary for BAAV infection or transcytosis, a glycan microarray composed of both natural and synthetic carbohydrates was probed with HA-tagged BAAV particles. This identified chitotriose, a trimer of β-1-4-linked N-acetyl glucosamine, as having an interaction with BAAV. Competition experiments showed that the BAAV interaction with this carbohydrate is not necessary for infection but is instead important in the transcytosis pathway. The β-1-4-linked N-acetyl glucosamine modification has been reported on gp96, a glycoprotein involved in the transcytosis of bacteria and toxins. Significantly, immunoprecipitation and competition experiments with an anti-gp96 antibody and a soluble form of gp96, respectively, showed this glycoprotein can also interact with BAAV to serve as a receptor for its transcytosis

Mechanisms of damage and repair in multiple sclerosis--a review.

Pathological features of MS include perivascular inflammation and demyelination with oligodendrocyte loss; in addition, attempts at remyelination are often unsuccessful and may culminate in astrocytic scarring. One approach to investigating the biological principles underlying these processes is to use in vitro systems to analyse single-cell behaviour as well as cell-cell interactions. This paper reviews such data concerned with cell injury and repair which illuminate both demyelination and remyelination. In tissue culture oligodendrocytes are susceptible to injury via cell-mediated and humoral mechanisms. Substances including complement and tumour necrosis factor are capable of killing rat oligodendrocytes in vitro; surface complement activation also initiates a number of intracellular processes within oligodendrocytes as well as providing ligands for phagocytic interactions. The reasons for oligodendrocyte complement activation are discussed, but it appears that species differences exist when extrapolating these data to humans. Myelination and remyelination can also be studied both in vitro and in vivo using defined cell populations. Results from these studies may eventually help to explain some pathological features of MS, including astrocytosis and factors governing the limits of remyelination.</p