Ferret models of viral pathogenesis.

Emerging and well-known viral diseases remain one the most important global public health threats. A better understanding of their pathogenesis and mechanisms of transmission requires animal models that accurately reproduce these aspects of the disease. Here we review the role of ferrets as an animal model for the pathogenesis of different respiratory viruses with an emphasis on influenza and paramyxoviruses. We will describe the anatomic and physiologic characteristics that contribute to the natural susceptibility of ferrets to these viruses, and provide an overview of the approaches available to analyze their immune responses. Recent insights gained using this model will be highlighted, including the development of new prophylactic and therapeutic approaches. To provide decision criteria for the use of this animal model, its strengths and limitations will be discussed.

Targeted lentiviral vectors pseudotyped with the Tupaia paramyxovirus glycoproteins.

Lentiviral vectors are vectors of choice for many gene therapy applications. Recently, efficient targeting of lentiviral vectors pseudotyped with the Measles virus (MV) glycoproteins has been reported. However, MV antibodies in patients might limit the clinical use of these vectors. We demonstrate here that lentiviral vectors can also be pseudotyped with the glycoproteins of Tupaia paramyxovirus (TPMV), the hemagglutinin (H) and fusion (F) protein. As this animal paramyxovirus has no known close relatives in humans, we do not expect TPMV antibodies in patients. Because TPMV normally does not infect human cells, 'detargeting' from natural receptors is unnecessary. Similar to the MV system, TPMV glycoproteins can mediate targeted cell entry by displaying different single-chain antibodies (scAb) directed against surface molecules on target cells on the viral hemagglutinin. We generated a panel of H and F proteins with truncated cytoplasmic tails and determined the variants that efficiently pseudotyped lentiviral vectors. The B-cell marker CD20 was used as a model antigen, and CD20-targeted TPMV vectors selectively transduced CD20-positive cells, including quiescent primary human B-cells. Lentiviral vectors pseudotyped with targeted TPMV envelope proteins might be a valuable vector choice when systemic application of targeted lentiviral vectors in humans is required.