Feline immunodeficiency virus (FIV) mainly infects monocytic cells and CD4+ T-cells. Once the virus gets into the cell, the genome is converted into DNA by a reverse transcriptase and is integrated into the cellular chromatin. The virus now relies on cellular transcription factors for its replication. Cats are infected during biting incidents. The virus in the saliva of the biting infected cat is transferred into the wound of the bitten cat. After a local replication, the virus is replicating in the draining lymph node and upon viremia in more distant lymphoid tissues. The replication of FIV appears to be blocked in infected monocytes and lymphocytes that circulate in blood. Upon arrival in the lymphoid tissues, a trigger activates the replication of the virus. Lymphoid tissues are an ideal replication site for the virus, with a lot of potential target cells and close cell contacts. The close cell targets can promote the formation of a viral synapse, a safe transfer zone for the virus in between cells. The first objective of the present project proposal is the isolation, immortalization and characterization of stromal cells derived from lymph node, spleen and red bone marrow. Second, FIV replication characteristics will be studied in monocytes, macrophages and lymphocytes, which are co-cultured with these stromal cells to simulate the in vivo situation in the lymphoid organs. The third objective will be the unmasking and manipulation of the cellular pathway(s) responsible for the observed effects and to identify the contribution of viral accessory proteins. . It is crucial to understand how viral replication occurs and its pathogenesis to make the proper diagnosis. The knowledge of pathogenesis is fundamental for the interpretation of diagnostic tests.Unraveling the mechanism(s) by which these stromal cells influence the FIV replication may provide new targets for antiviral therapy.
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