Abstracts from the 14th International Symposium on NeuroVirology October 25–28, 2016, Toronto, Ontario, Canada


s from the 14th International Symposium on NeuroVirology October 25–28, 2016, Toronto, Ontario, Canada Published online: 27 September 2016 # Journal of NeuroVirology, Inc. 2016 P1 Comparative Modeling of Human Endogenous Retrovirus-K Protease Based on HIV Protease Predicts Efficacy of Protease Inhibitors Rachel Abrams, Richa Tyagi,Wenxue Li, Mario Bianchet, Avindra Nath (corresponding author: rachel.abrams@nih.gov) National Institute of Neurological Disorders and Stroke, National Institutes of Health; Department of Neurology, Johns Hopkins School of Medicine Over the course of human evolution, retroviruses have infected cells of the germ line, allowing the genome of the virus to be passed down from parent to offspring. These human endogenous retroviruses (HERVs) make up about 8 % of the genome; however, in most cases multiple mutations have made them inactive. One of the most recently incorporated (HERV-K); however, has been implicated in the development of amyotrophic lateral sclerosis (ALS). Increased expression of HERV-K viral transcripts was observed in the brains of ALS patients and the expression of HERV-K envelope causes damage to motor neurons in vivo. While there are no treatment options for patients with ALS, in some patients with HIV infection that also display an ALS-like syndrome, antiretroviral drugs can reverse the ALS symptoms. Both HIV and HERV-K utilize an aspartic acid protease to process the viral polyprotein to its active components. To determine if HIV protease inhibitors could inhibit HERV-K protease, HIV protease inhibitors were tested in an in vitro HERVK infection model. The compounds tested had a moderate protective effect; however, were less effective than against HIV infection. To investigate the reason for the level of observed inhibition, similarities and differences between HIV and HERV-K protease were examined. There is no crystal structure of the HERV-K protease available, hence comparative modeling using the sequence alignment with HIV protease was performed. A homology model was generated and refined using the Prime program in the Schrodinger Suites Software package. This model was used to compare the active site of HIV protease with that of HERV-K. It can be seen from the model that while the overall structures of the proteases appear quite similar, changes in the active pocket caused by the few amino acid differences may be sufficient to explain the observed reduction in antiviral activity. P2 Role of ATF6b in HIV-Associated Neurocognitive Disorders Cagla Akay Espinoza, Ping Lin (corresponding author: akayc@upenn.edu) University of Pennsylvania, School of Dental Medicine, Department of Pathology The underlying mechanism of cognitive impairment and b r a i n i n j u r y i n pa t i e n t s w i t h HIV-a s soc i a t ed neurocognitive disorder (HAND) on suppressive antiretroviral therapy are not completely understood. However, synaptic injury, neuronal dysfunction, and damage in these patients are partially driven by immune activation and chronic inflammation in response to soluble factors released by HIV-infected and/or activated macrophages as well as a low level of HIV replication in central nervous system (CNS) reservoirs. A majority of these mediators as J. Neurovirol. (2016) 22 (Suppl 1):S1–S89 DOI 10.1007/s13365-016-0478-8

DOI: 10.1007/s13365-016-0478-8

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@article{Abrams2016AbstractsFT, title={Abstracts from the 14th International Symposium on NeuroVirology October 25–28, 2016, Toronto, Ontario, Canada}, author={Rachel P. M. Abrams and Richa Tyagi and Wenxue and Mario A Bianchet and Avindra Nath and Cagla Akay Espinoza and Ping Lin}, journal={Journal of NeuroVirology}, year={2016}, volume={22}, pages={1-89} }