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Open AccessArticle

Genome Analysis and Replication Studies of the African Green Monkey Simian Foamy Virus Serotype 3 Strain FV2014

1
Laboratory of Retroviruses, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Review, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
2
Current Address: Ross University School of Medicine, Miramar, FL 33027, USA
3
Current Address: Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
4
Present Address: Office of Device Evaluation, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(4), 403; https://doi.org/10.3390/v12040403
Received: 30 December 2019 / Revised: 27 January 2020 / Accepted: 1 April 2020 / Published: 6 April 2020
(This article belongs to the Special Issue Spumaretroviruses)
African green monkey (AGM) spumaretroviruses have been less well-studied than other simian foamy viruses (SFVs). We report the biological and genomic characterization of SFVcae_FV2014, which was the first foamy virus isolated from an African green monkey (AGM) and was found to be serotype 3. Infectivity studies in various cell lines from different species (mouse, dog, rhesus monkey, AGM, and human) indicated that like other SFVs, SFVcae_FV2014 had broad species and cell tropism, and in vitro cell culture infection resulted in cytopathic effect (CPE). In Mus dunni (a wild mouse fibroblast cell line), MDCK (Madin-Darby canine kidney cell line), FRhK-4 (a fetal rhesus kidney cell line), and MRC-5 (a human fetal lung cell line), SFVcae_FV2014 infection was productive resulting in CPE, and had delayed or similar replication kinetics compared with SFVmcy_FV21 and SFVmcy_FV34[RF], which are two Taiwanese macaque isolates, designated as serotypes 1 and 2, respectively. However, in Vero (AGM kidney cell line) and A549 (a human lung carcinoma cell line), the replication kinetics of SFVcae_FV2014 and the SFVmcy viruses were discordant: In Vero, SFVcae_FV2014 showed rapid replication kinetics and extensive CPE, and a persistent infection was seen in A549, with delayed, low CPE, which did not progress even upon extended culture (day 55). Nucleotide sequence analysis of the assembled SFVcae_FV2014 genome, obtained by high-throughput sequencing, indicated an overall 80–90% nucleotide sequence identity with SFVcae_LK3, the only available full-length genome sequence of an AGM SFV, and was distinct phylogenetically from other AGM spumaretroviruses, corroborating previous results based on analysis of partial env sequences. Our study confirmed that SFVcae_FV2014 and SFVcae_LK3 are genetically distinct AGM foamy virus (FV) isolates. Furthermore, comparative infectivity studies of SFVcae_FV2014 and SFVmcy isolates showed that although SFVs have a wide host range and cell tropism, regulation of virus replication is complex and depends on the virus strain and cell-specific factors. View Full-Text
Keywords: simian foamy virus; spumaretrovirus; serotype; high-throughput sequencing; replication kinetics; cytopathic effect; reverse transcriptase activity simian foamy virus; spumaretrovirus; serotype; high-throughput sequencing; replication kinetics; cytopathic effect; reverse transcriptase activity
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Fuentes, S.M.; Bae, E.H.; Nandakumar, S.; Williams, D.K.; Khan, A.S. Genome Analysis and Replication Studies of the African Green Monkey Simian Foamy Virus Serotype 3 Strain FV2014. Viruses 2020, 12, 403.

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