title: In Vitro Evolution of Bovine Foamy Virus Variants with Enhanced Cell-Free Virus Titers and Transmission.
abstract: Virus transmission is essential for spreading viral infections and is a highly coordinated process which occurs by cell-free transmission or cell-cell contact. The transmission of Bovine Foamy Virus (BFV) is highly cell-associated, with undetectable cell-free transmission. However, BFV particle budding can be induced by overexpression of wild-type (wt) BFV Gag and Env or artificial retargeting of Gag to the plasma membrane via myristoylation membrane targeting signals, closely resembling observations in other foamy viruses. Thus, the particle release machinery of wt BFV appears to be an excellent model system to study viral adaption to cell-free transmission by in vitro selection and evolution. Using selection for BFV variants with high cell-free infectivity in bovine and non-bovine cells, infectivity dramatically increased from almost no infectious units to about 105-106 FFU (fluorescent focus forming units)/mL in both cell types. Importantly, the selected BFV variants with high titer (HT) cell-free infectivity could still transmit via cell-cell contacts and were neutralized by serum from naturally infected cows. These selected HT-BFV variants will shed light into virus transmission and potential routes of intervention in the spread of viral infections. It will also allow the improvement or development of new promising approaches for antiretroviral therapies.
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. q.bao@dkfz.de.
authors.forename: Qiuying
authors.initials: Q
authors.lastname: Bao
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. m.hipp@dkfz.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Hipp
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. a.hugo@dkfz.de.
authors.forename: Annette
authors.initials: A
authors.lastname: Hugo
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. janet.lei@oncology.ox.ac.uk.|Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. janet.lei@oncology.ox.ac.uk.
authors.forename: Janet
authors.initials: J
authors.lastname: Lei
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. liuy18@nih.gov.|Department Viral Recombination, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. liuy18@nih.gov.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. t.kehl@dkfz.de.
authors.forename: Timo
authors.initials: T
authors.lastname: Kehl
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. t.hechler@hdpharma.com.|Heidelberg Pharma GmbH, 68526 Ladenburg, Germany. t.hechler@hdpharma.com.
authors.forename: Torsten
authors.initials: T
authors.lastname: Hechler
authors.affiliation: Division of Molecuar Diagnostics of Oncogenic Infections, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 242, 69120, Germany. m.loechelt@dkfz.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Löchelt
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D005075:Biological Evolution; D002478:Cells, Cultured; D006801:Humans; D008954:Models, Biological; D012192:Retroviridae Infections / Q000635:transmission* / Q000662:veterinary* / Q000821:virology; D012641:Selection, Genetic; D016092:Spumavirus / Q000235:genetics* / Q000254:growth & development*; D019562:Viral Load; D053586:Virus Internalization; D057074:Virus Release
keywords: Gag myristoylation; bovine foamy virus; particle release; retrovirus; virus budding; virus transmission