Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry

0486607 - ÚMG 2019 US eng J - Journal Article
Lounková, Anna - Kosla, Jan - Přikryl, David - Štafl, Kryštof - Kučerová, Dana - Svoboda, Jan
Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 114, č. 26 (2017), E5148-E5157. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA ČR GA15-22207S; GA MŠMT LO1419
Institutional support: RVO:68378050
Keywords : Rous sarcoma virus * retrovirus * virus entry * envelope glycoprotein * receptor-independent entry
OECD category: Virology
Impact factor: 9.504, year: 2017

The extent of virus transmission among individuals and species is generally determined by the presence of specific membrane-embedded virus receptors required for virus entry. Interaction of the viral envelope glycoprotein (Env) with a specific cellular receptor is the first and crucial step in determining host specificity. Using a well-established retroviral model-avian Rous sarcoma virus (RSV)-we analyzed changes in an RSV variant that had repeatedly been able to infect rodents. By envelope gene (env) sequencing, we identified eight mutations that do not match the already described mutations influencing the host range. Two of these mutations-one at the beginning (D32G) of the surface Env subunit (SU) and the other at the end of the fusion peptide region (L378S)-were found to be of critical importance, ensuring transmission to rodent, human, and chicken cells lacking the appropriate receptor. Furthermore, we carried out assays to examine the virus entry mechanism and concluded that these two mutations cause conformational changes in the Env variant and that these changes lead to an activated, or primed, state of Env (normally induced after Env interaction with the receptor). In summary, our results indicate that retroviral host range extension is caused by spontaneous Env activation, which circumvents the need for original cell receptor. This activation is, in turn, caused by mutations in various env regions.
Permanent Link: http://hdl.handle.net/11104/0281371