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item Mecham, James

Submitted to: Immunology Research Workshop
Publication Type: Abstract Only
Publication Acceptance Date: 12/3/2003
Publication Date: 12/3/2003
Citation: Mecham, J.O. 2003. Neutralization of bluetongue virus in vertebrate and invertebrate cells. 2003 ARS Immunology Research Workshop.

Interpretive Summary: Bluetongue virus (BTV) is an orbivirus that infects sheep, cattle and wild ruminants. It is transmitted by biting midges in the genus Culicoides. Infection of the mammalian host results in the production of neutralizing antibody that clears the virus. It has been shown that BTV associates with erythrocytes, which results in an extended viremia in the infected host. This extended viremia may also be important in transmission of the virus via the insect vector. Infection of vertebrates and insects by BTV appears to occur by different mechanisms; therefore, the presence of neutralizing antibody in the infected vertebrate may not prevent infection of the insect vector. If this is the case, traditional approaches to immunization may not successfully interrupt the transmission cycle of BTV. To examine this question, the effect of neutralizing antibodies on BTV infection of cell lines derived from Culicoides was examined. The results suggest that neutralizing antibody does not inhibit infection and/or replication of BTV in these insect cells. However, non-neutralizing antibody to BTV did inhibit replication in these cells and suggests an alternative approach to vaccination to interrupt the transmission cycle of BTV

Technical Abstract: Bluetongue virus (BTV) is an orbivirus that infects sheep, cattle and wild ruminants. It is transmitted to susceptible vertebrate hosts by biting midges in the genus Culicoides. Following infection, the vertebrate host produces neutralizing antibodies that are responsible for virus clearance and conferring immunity to subsequent virus challenge. These neutralizing antibodies are directed against the virus outer capsid, which is also responsible for initiating infection in the vertebrate host. Infection of the insect vector is believed to be mediated primarily by the inner capsid, which is not the target of neutralizing antibody. Therefore, virus that is neutralized for infection of vertebrate cells may still be infectious for invertebrate cells. This may have important implications in the natural epidemiology of BTV infections. To investigate this further, the mechanisms of neutralization of BTV in both vertebrate and invertebrate cells was investigated. Antibodies that neutralize BTV infection in vertebrate cells failed to neutralize viral infection in a Culicoides cell line. However, non-neutralizing antibodies that react with a virus core protein inhibited infection and/or replication of BTV in the Culicoides cell line. Since this virus core protein is highly conserved between BTV serotypes, and appears to play an important role in the initiation of BTV infection in insect cells, it may represent a novel target for control of infection caused by these viruses.