Pathogenesis And Immunology Of Animal And Human Retroviruses

在过去的几年里，我们一直在研究Fr98小鼠逆转录病毒株引起的脑部疾病。在2008年，我们的实验确定了Fr98小鼠逆转录病毒包膜中的氨基酸残基，这些氨基酸残基是由该病毒诱导的脑部疾病所必需的。这些残基位于线性蛋白序列的几个不同位置。当基于一种密切相关的小鼠逆转录病毒的晶体结构在三维空间中观察包膜前蛋白结构时，这些氨基酸位于两个不同的组中。这些结果支持了包膜蛋白表面的两个独立区域协同影响逆转录病毒的神经发病机制的观点。

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.