Number of the records: 1
Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry
- 1.
SYSNO ASEP 0486607 Document Type J - Journal Article R&D Document Type The record was not marked in the RIV Subsidiary J Článek ve WOS Title Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry Author(s) Lounková, Anna (UMG-J)
Kosla, Jan (UMG-J) RID
Přikryl, David (UMG-J)
Štafl, Kryštof (UMG-J)
Kučerová, Dana (UMG-J)
Svoboda, Jan (UMG-J) RIDNumber of authors 6 Source Title Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences - ISSN 0027-8424
Roč. 114, č. 26 (2017), E5148-E5157Number of pages 10 s. Language eng - English Country US - United States Keywords Rous sarcoma virus ; retrovirus ; virus entry ; envelope glycoprotein ; receptor-independent entry Subject RIV EB - Genetics ; Molecular Biology OECD category Virology R&D Projects GA15-22207S GA ČR - Czech Science Foundation (CSF) LO1419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000404108400018 DOI https://doi.org/10.1073/pnas.1704750114 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2019
Number of the records: 1