NAS on WIV1 (SARS-2), 2016-03
https://sites.google.com/site/zhiyanleback/data01/nas-201603-wiv1
Assessing emergence of SARS-like epidemic viruses
PNAS March 15, 2016 113 (11) 2793-2795;
https://doi.org/10.1073/iti1116113
The precise likelihood of emergence of zoonotic coronaviruses with epidemic potential similar to severe acute respiratory coronavirus (SARS-CoV) remains unclear. Using a reverse genetics approach, Vineet Menachery et al. (pp. 3048–3053) constructed WIV1-CoV, a previously described bat coronavirus that can infect humans using the human angiotensin converting enzyme 2 (ACE2), as well as a hybrid virus containing the WIV1-CoV surface spike protein in a SARS-CoV backbone adapted for murine infection.
The authors found that both engineered viruses robustly infected human lung airway epithelial cultures, suggesting that the WIV1-CoV spike protein can mediate human infection without further molecular adaptations. Compared with SARS-CoV, WIV1-CoV displayed weakened replication in wild-type mice.
Although WIV1-CoV replication improved in mice engineered to express human ACE2, it failed to reach levels comparable to that of the epidemic SARS-CoV.
Importantly, a broadly neutralizing monoclonal antibody panel derived from phage display and B cells of patients infected with SARS-CoV protected mice against potentially lethal exposure to both SARS-CoV and wild-type WIV1-CoV.
Compared with mock-treated mice, mice that were administered the protective antibodies harbored no detectable virus in the lungs.
However, a double-inactivated SARS-CoV candidate vaccine, previously found to be effective in young mice, failed to protect mice against a WIV1-CoV challenge. According to the authors, compared with SARS-CoV, WIV1-CoV might pose a diminished epidemic threat to humans, warranting studies on its zoonotic potential. — P.N.
SARS-like WIV1-CoV poised for human emergence
PNAS March 15, 2016 113 (11) 3048-3053;
first published March 14, 2016 / (received for review September 4, 2015)
https://doi.org/10.1073/pnas.1517719113
https://www.pnas.org/content/113/11/3048
Significance
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV highlights the continued risk of cross-species transmission leading to epidemic disease. This manuscript describes efforts to extend surveillance beyond sequence analysis, constructing chimeric and full-length zoonotic coronaviruses to evaluate emergence potential. Focusing on SARS-like virus sequences isolated from Chinese horseshoe bats, the results indicate a significant threat posed by WIV1-CoV. Both full-length and chimeric WIV1-CoV readily replicated efficiently in human airway cultures and in vivo, suggesting capability of direct transmission to humans. In addition, while monoclonal antibody treatments prove effective, the SARS-based vaccine approach failed to confer protection. Together, the study indicates an ongoing threat posed by WIV1-related viruses and the need for continued study and surveillance.
Abstract
Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.
Construction of Chimeric SARS-Like Viruses.
Both wild-type and chimeric WIV-CoV infectious clones were designed using published sequences and based on the SARS-CoV infectious clone (10). Synthetic construction of chimeric mutant and full-length WIV1-CoV were approved by the UNC Institutional Biosafety Committee and the Dual Use Research of Concern Committee.
Acknowledgments
We thank Dr. Zhengli-Li Shi of the Wuhan Institute of Virology for access to bat CoV sequences and plasmid of WIV1-CoV spike protein. Research was supported by the National Institute of Allergy and Infectious Disease and the National Institute of Aging of the NIH under Awards U19AI109761 and U19AI107810 (to R.S.B.), AI1085524 (to W.A.M.), and F32AI102561 and K99AG049092 (to V.D.M.). Human airway epithelial cell cultures were supported by the National Institute of Diabetes and Digestive and Kidney Disease under Award NIH DK065988 (to S.H.R.). Support for the generation of the mice expressing human ACE2 was provided by NIH Grants AI076159 and AI079521 (to A.C.S.).