Pathogenesis And Immunology Of Animal And Human Retroviruses

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For the past several years wwe having been studying brain disease induced by the Fr98 strain of mouse retrovirus. In FY08 our experiments identified the amino acid residues in the envelope of the Fr98 mouse retrovirus which were required for the brain disease induced by this virus. These residues were located in several separate locations in the linear protein sequence. When the envelope preotein structure was viewed in 3-dimensions based on the crystal structure of a closely related mouse retrovirus, these amino acids were located in two distinct groups. These results supported the idea that two separate areas of the surface of the envelope protein cooperatively influence the neuropathogenesis of this retrovirus. In FY08 our group collaborated with the laboratories of Dr Kim Hasenkrug at LPVD and Dr Warner Greene at UCSF to demonstrate that the Rfv-3 gene discovered in 1978 at LPVD was identical to the APOBEC3 gene which is currently under intense study in the HIV field. These results indicated that APOBEC3 appeared to have previously unsuspected effects on the immune response to retroviruses.