Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission

View ORCID ProfileChao Shan, View ORCID ProfileHongjie Xia, View ORCID ProfileSherry L. Haller, View ORCID ProfileSasha R. Azar, Yang Liu, Jianying Liu, Antonio E. Muruato, Rubing Chen, Shannan L. Rossi, View ORCID ProfileMaki Wakamiya, View ORCID ProfileNikos Vasilakis, Rongjuan Pei, Camila R. Fontes-Garfias, Sanjay Kumar Singh, Xuping Xie, View ORCID ProfileScott C. Weaver, and Pei-Yong Shi
PNAS August 18, 2020 117 (33) 20190-20197; first published August 3, 2020; https://doi.org/10.1073/pnas.2005722117
Chao Shan
aDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555;
bState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 430071 Wuhan, China;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Chao Shan
  • For correspondence: shanchao@wh.iov.cn sweaver@UTMB.edu peshi@UTMB.edu
Hongjie Xia
aDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hongjie Xia
Sherry L. Haller
cDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
eInstitute for Translational Science, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sherry L. Haller
Sasha R. Azar
cDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
eInstitute for Translational Science, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sasha R. Azar
Yang Liu
aDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianying Liu
cDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Antonio E. Muruato
cDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rubing Chen
cDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
eInstitute for Translational Science, University of Texas Medical Branch, Galveston, TX 77555;
fDepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shannan L. Rossi
cDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
fDepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maki Wakamiya
aDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maki Wakamiya
Nikos Vasilakis
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
fDepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555;
gWorld Reference Center of Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555;
hCenter for Biodefence and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555;
iCenter for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nikos Vasilakis
Rongjuan Pei
bState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 430071 Wuhan, China;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Camila R. Fontes-Garfias
aDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sanjay Kumar Singh
jDepartment of Neurosurgery-Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xuping Xie
aDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott C. Weaver
cDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
eInstitute for Translational Science, University of Texas Medical Branch, Galveston, TX 77555;
kSealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555;
lSealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Scott C. Weaver
  • For correspondence: shanchao@wh.iov.cn sweaver@UTMB.edu peshi@UTMB.edu
Pei-Yong Shi
aDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555;
dInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555;
eInstitute for Translational Science, University of Texas Medical Branch, Galveston, TX 77555;
kSealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555;
lSealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: shanchao@wh.iov.cn sweaver@UTMB.edu peshi@UTMB.edu
  1. Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved July 2, 2020 (received for review March 26, 2020)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

ZIKV has “silently” circulated without causing severe diseases for decades since its discovery in 1947. Our study demonstrated that ZIKV acquired an evolutionary mutation in viral envelope gene (E-V473M) that increases virulence, maternal-to-fetal transmission during pregnancy, and viremia in nonhuman primates to facilitate urban transmission since 2013, which may be responsible for the recent emergence and severe diseases. Our results underscore the potential that high genetic mutation frequencies during arbovirus replication and transmission between mosquito and vertebrate hosts could lead to emergence and reemergence of those pathogens. Understanding the mechanisms of emergence and enhanced transmission is essential to detect and respond to future arbovirus outbreaks.

Abstract

Arboviruses maintain high mutation rates due to lack of proofreading ability of their viral polymerases, in some cases facilitating adaptive evolution and emergence. Here we show that, just before its 2013 spread to the Americas, Zika virus (ZIKV) underwent an envelope protein V473M substitution (E-V473M) that increased neurovirulence, maternal-to-fetal transmission, and viremia to facilitate urban transmission. A preepidemic Asian ZIKV strain (FSS13025 isolated in Cambodia in 2010) engineered with the V473M substitution significantly increased neurovirulence in neonatal mice and produced higher viral loads in the placenta and fetal heads in pregnant mice. Conversely, an epidemic ZIKV strain (PRVABC59 isolated in Puerto Rico in 2015) engineered with the inverse M473V substitution reversed the pathogenic phenotypes. Although E-V473M did not affect oral infection of Aedes aegypti mosquitoes, competition experiments in cynomolgus macaques showed that this mutation increased its fitness for viremia generation, suggesting adaptive evolution for human viremia and hence transmission. Mechanistically, the V473M mutation, located at the second transmembrane helix of the E protein, enhances virion morphogenesis. Overall, our study revealed E-V473M as a critical determinant for enhanced ZIKV virulence, intrauterine transmission during pregnancy, and viremia to facilitate urban transmission.

  • Zika
  • envelope
  • evolution
  • transmission

Footnotes

  • ↵1C.S. and H.X. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: shanchao{at}wh.iov.cn, sweaver{at}UTMB.edu, or peshi{at}UTMB.edu.
  • Author contributions: C.S., H.X., S.L.H., S.R.A., Y.L., S.L.R., N.V., X.X., S.C.W., and P.-Y.S. designed research; C.S., H.X., S.L.H., S.R.A., Y.L., J.L., A.E.M., R.C., S.L.R., M.W., N.V., R.P., C.R.F.-G., S.K.S., and X.X. performed research; C.S., H.X., S.L.H., S.R.A., Y.L., J.L., A.E.M., R.C., S.L.R., M.W., N.V., R.P., C.R.F.-G., S.K.S., X.X., S.C.W., and P.-Y.S. analyzed data; and C.S., H.X., S.L.H., S.R.A., S.C.W., and P.-Y.S. wrote the paper.

  • The authors declare no competing interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2005722117/-/DCSupplemental.

Data Availability.

Source data for generating main figures are available in the SI Appendix.

Published under the PNAS license.

View Full Text

References

  1. ↵
    1. G. W. Dick,
    2. S. F. Kitchen,
    3. A. J. Haddow
    , Zika virus. I. Isolations and serological specificity. Trans. R. Soc. Trop. Med. Hyg. 46, 509–520 (1952).
    OpenUrlCrossRefPubMed
  2. ↵
    1. D. Musso,
    2. D. J. Gubler
    , Zika virus. Clin. Microbiol. Rev. 29, 487–524 (2016).
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. S. A. Rasmussen,
    2. D. J. Jamieson,
    3. M. A. Honein,
    4. L. R. Petersen
    , Zika virus and birth defects—Reviewing the evidence for causality. N. Engl. J. Med. 374, 1981–1987 (2016).
    OpenUrlCrossRefPubMed
  4. ↵
    1. P. Brasil et al.
    , Zika virus infection in pregnant women in Rio de Janeiro. N. Engl. J. Med. 375, 2321–2334 (2016).
    OpenUrlPubMed
  5. ↵
    1. V. M. Cao-Lormeau et al.
    , Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study. Lancet 387, 1531–1539 (2016).
    OpenUrlCrossRefPubMed
  6. ↵
    1. D. M. Knipe,
    2. P. M. Howley
    1. T. C. Pierson,
    2. M. S. Diamond,
    “Flaviviruses” in Fields Virology, D. M. Knipe, P. M. Howley, Eds. (Lippincott Williams & Wilkins, ed. 6, 2013), Vol. vol. 1, pp. 747–794.
    OpenUrl
  7. ↵
    1. C. L. Murray,
    2. C. T. Jones,
    3. C. M. Rice
    , Architects of assembly: Roles of flaviviridae non-structural proteins in virion morphogenesis. Nat. Rev. Microbiol. 6, 699–708 (2008).
    OpenUrlCrossRefPubMed
  8. ↵
    1. X. Zhang et al.
    , Zika virus NS2A-mediated virion assembly. MBio 10, e02375-19 (2019).
    OpenUrl
  9. ↵
    1. X. Xie et al.
    , Dengue NS2A protein orchestrates virus assembly. Cell Host Microbe 26, 606–622.e8 (2019).
    OpenUrl
  10. ↵
    1. J. H. Pettersson et al.
    , How did Zika virus emerge in the Pacific Islands and Latin America? MBio 7, e01239-16 (2016).
    OpenUrlCrossRef
  11. ↵
    1. H. Xia et al.
    , An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. Nat. Commun. 9, 414–427 (2018).
    OpenUrlCrossRef
  12. ↵
    1. Y. Liu et al.
    , Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature 545, 482–486 (2017).
    OpenUrlCrossRefPubMed
  13. ↵
    1. L. Yuan et al.
    , A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science 358, 933–936 (2017).
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. A. S. Jaeger et al.
    , Zika viruses of African and Asian lineages cause fetal harm in a mouse model of vertical transmission. PLoS Negl. Trop. Dis. 13, e0007343 (2019).
    OpenUrlCrossRef
  15. ↵
    1. C. Shan et al.
    , An infectious cDNA clone of Zika virus to study viral virulence, mosquito transmission, and antiviral inhibitors. Cell Host Microbe 19, 891–900 (2016).
    OpenUrlCrossRefPubMed
  16. ↵
    1. S. L. Rossi et al.
    , Characterization of a novel murine model to study Zika virus. Am. J. Trop. Med. Hyg. 94, 1362–1369 (2016).
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. H. M. Lazear et al.
    , A mouse model of Zika virus pathogenesis. Cell Host Microbe 19, 720–730 (2016).
    OpenUrlCrossRefPubMed
  18. ↵
    1. S. R. Azar,
    2. E. E. Diaz-Gonzalez,
    3. R. Danis-Lonzano,
    4. I. Fernandez-Salas,
    5. S. C. Weaver
    , Naturally infected Aedes aegypti collected during a Zika virus outbreak have viral titres consistent with transmission. Emerg. Microbes Infect. 8, 242–244 (2019).
    OpenUrlCrossRef
  19. ↵
    1. C. R. Fontes-Garfias et al.
    , Functional analysis of glycosylation of Zika virus envelope protein. Cell Rep. 21, 1180–1190 (2017).
    OpenUrlCrossRefPubMed
  20. ↵
    1. D. Sirohi et al.
    , The 3.8 Å resolution cryo-EM structure of Zika virus. Science 352, 467–470 (2016).
    OpenUrlAbstract/FREE Full Text
  21. ↵
    1. V. A. Kostyuchenko et al.
    , Structure of the thermally stable Zika virus. Nature 533, 425–428 (2016).
    OpenUrlCrossRefPubMed
  22. ↵
    1. J. V. J. Silva,
    2. T. R. R. Lopes,
    3. E. F. Oliveira-Filho,
    4. R. A. D. S. Oliveira,
    5. L. H. V. G. Gil
    , Perspectives on the Zika outbreak: Herd immunity, antibody-dependent enhancement and vaccine. Rev. Inst. Med. Trop. São Paulo 59, e21 (2017).
    OpenUrl
  23. ↵
    1. M. G. Zimmerman et al.
    , Cross-reactive Dengue virus antibodies augment Zika virus infection of human placental macrophages. Cell Host Microbe 24, 731–742.e6 (2018).
    OpenUrlCrossRef
  24. ↵
    1. V. N. Camargos et al.
    , In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapy. EBioMedicine 44, 516–529 (2019).
    OpenUrl
  25. ↵
    1. J. A. Brown et al.
    , Dengue virus immunity increases Zika virus-induced damage during pregnancy. Immunity 50, 751–762.e5 (2019).
    OpenUrlCrossRef
  26. ↵
    1. A. M. Fowler et al.
    , Maternally acquired Zika antibodies enhance Dengue disease severity in mice. Cell Host Microbe 24, 743–750.e5 (2018).
    OpenUrlCrossRef
  27. ↵
    1. S. V. Bardina et al.
    , Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity. Science 356, 175–180 (2017).
    OpenUrlAbstract/FREE Full Text
  28. ↵
    1. L. R. Petersen,
    2. D. J. Jamieson,
    3. M. A. Honein
    , Zika virus. N. Engl. J. Med. 375, 294–295 (2016).
    OpenUrlCrossRef
  29. ↵
    1. L. C. Caires-Júnior et al.
    , Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells. Nat. Commun. 9, 475–486 (2018).
    OpenUrlCrossRefPubMed
  30. ↵
    1. S. C. Weaver
    , Emergence of epidemic Zika virus transmission and congenital Zika syndrome: Are recently evolved traits to blame? MBio 8, e02063-16 (2017).
    OpenUrlCrossRef
  31. ↵
    1. H. Xia,
    2. X. Xie,
    3. C. Shan,
    4. P. Y. Shi
    , Potential mechanisms for enhanced Zika epidemic and disease. ACS Infect. Dis. 4, 656–659 (2018).
    OpenUrl
  32. ↵
    1. S. C. Weaver,
    2. W. K. Reisen
    , Present and future arboviral threats. Antiviral Res. 85, 328–345 (2010).
    OpenUrlCrossRefPubMed
  33. ↵
    1. National Research Council of the National Academies
    , Guide for the Care and Use of Laboratory Animals, (The National Academies Press, Washington, DC, 8th Ed., 2011).
  34. ↵
    1. S. L. Rossi et al.
    , Immunogenicity and efficacy of a measles virus-vectored chikungunya vaccine in nonhuman primates. J. Infect. Dis. 220, 735–742 (2019).
    OpenUrl
  35. ↵
    1. C. Shan et al.
    , A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models. Nat. Med. 23, 763–767 (2017).
    OpenUrlCrossRefPubMed
  36. ↵
    1. J. M. Richner et al.
    , Vaccine mediated protection against Zika virus-induced congenital disease. Cell 170, 273–283.e12 (2017).
    OpenUrlCrossRef
  37. ↵
    1. Y. Yang et al.
    , A cDNA clone-launched platform for high-yield production of inactivated Zika vaccine. EBioMedicine 17, 145–156 (2017).
    OpenUrl

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.

Subscribers, for more details, please visit our Subscriptions FAQ.

Please click here to log into the PNAS submission website.

PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission
Chao Shan, Hongjie Xia, Sherry L. Haller, Sasha R. Azar, Yang Liu, Jianying Liu, Antonio E. Muruato, Rubing Chen, Shannan L. Rossi, Maki Wakamiya, Nikos Vasilakis, Rongjuan Pei, Camila R. Fontes-Garfias, Sanjay Kumar Singh, Xuping Xie, Scott C. Weaver, Pei-Yong Shi
Proceedings of the National Academy of Sciences Aug 2020, 117 (33) 20190-20197; DOI: 10.1073/pnas.2005722117

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission
Chao Shan, Hongjie Xia, Sherry L. Haller, Sasha R. Azar, Yang Liu, Jianying Liu, Antonio E. Muruato, Rubing Chen, Shannan L. Rossi, Maki Wakamiya, Nikos Vasilakis, Rongjuan Pei, Camila R. Fontes-Garfias, Sanjay Kumar Singh, Xuping Xie, Scott C. Weaver, Pei-Yong Shi
Proceedings of the National Academy of Sciences Aug 2020, 117 (33) 20190-20197; DOI: 10.1073/pnas.2005722117
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 117 (33)
Table of Contents

Submit

Sign up for Article Alerts

Article Classifications

  • Biological Sciences
  • Microbiology

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Data Availability.
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Large piece of gold
News Feature: Tracing gold's cosmic origins
Astronomers thought they’d finally figured out where gold and other heavy elements in the universe came from. In light of recent results, they’re not so sure.
Image credit: Science Source/Tom McHugh.
Dancers in red dresses
Journal Club: Friends appear to share patterns of brain activity
Researchers are still trying to understand what causes this strong correlation between neural and social networks.
Image credit: Shutterstock/Yeongsik Im.
White and blue bird
Hazards of ozone pollution to birds
Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490