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发帖数: 1 | 1 A SARS-like cluster of circulating bat coronaviruses shows potential for
human emergence
https://www.nature.com/articles/nm.3985#article-info
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV)
and Middle East respiratory syndrome (MERS)-CoV underscores the threat of
cross-species transmission events leading to outbreaks in humans. Here we
examine the disease potential of a SARS-like virus, SHC014-CoV, which is
currently circulating in Chinese horseshoe bat populations1. Using the SARS-
CoV reverse genetics system2, we generated and characterized a chimeric
virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS
-CoV backbone. The results indicate that group 2b viruses encoding the
SHC014 spike in a wild-type backbone can efficiently use multiple orthologs
of the SARS receptor human angiotensin converting enzyme II (ACE2),
replicate efficiently in primary human airway cells and achieve in vitro
titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo
experiments demonstrate replication of the chimeric virus in mouse lung with
notable pathogenesis. Evaluation of available SARS-based immune-therapeutic
and prophylactic modalities revealed poor efficacy; both monoclonal
antibody and vaccine approaches failed to neutralize and protect from
infection with CoVs using the novel spike protein. On the basis of these
findings, we synthetically re-derived an infectious full-length SHC014
recombinant virus and demonstrate robust viral replication both in vitro and
in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from
viruses currently circulating in bat populations. | b*********4
发帖数: 1 | 2 For Americans:
we built a (chimeric) virus | b*********4
发帖数: 1 | 3 A SARS-like cluster of circulating bat coronaviruses shows potential for
human emergence
Vineet D Menachery,
Boyd L Yount Jr,
Kari Debbink,
Sudhakar Agnihothram,
Lisa E Gralinski,
Jessica A Plante,
Rachel L Graham,
Trevor Scobey,
Xing-Yi Ge,
Eric F Donaldson,
Scott H Randell,
Antonio Lanzavecchia,
Wayne A Marasco,
Zhengli-Li Shi &
Ralph S Baric | b*********4
发帖数: 1 | 4 Created in lab:
we built a chimeric virus encoding a novel, zoonotic CoV spike protein—from
the RsSHC014-CoV sequence that was isolated from Chinese horseshoe bats1—
in the context of the SARS-CoV mouse-adapted backbone. The hybrid virus
allowed us to evaluate the ability of the novel spike protein to cause
disease independently of other necessary adaptive mutations in its natural
backbone.
Female, 10-week-old and 12-month-old BALB/cAnNHsD mice were ordered from
Harlan Laboratories. Mouse infections were done as previously described20.
Briefly, animals were brought into a BSL3 laboratory and allowed to
acclimate for 1 week before infection. |
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