Shi Zhengli
Shi Zhengli is a Chinese virologist who directs the Center for Emerging Infectious Diseases at the Wuhan Institute of Virology, where her laboratory investigates bat-borne viruses, particularly coronaviruses with potential for interspecies transmission.[1] Her research has focused on identifying SARS-like coronaviruses in horseshoe bats, establishing them as natural reservoirs capable of harboring viruses genetically close to those causing human outbreaks.[2][3] Key achievements include isolating bat SARS-like coronavirus WIV1, which was shown to infect human airway cells and exhibit limited airborne transmission in animal models, indicating preparedness for zoonotic spillover without prior adaptation.[4][5] She co-authored studies on chimeric constructs combining bat coronavirus spike proteins with SARS-CoV backbones, demonstrating enhanced viral entry into human cells via receptor binding similar to SARS-CoV.[6] These findings, derived from field sampling in Chinese bat caves, underscored the pandemic risk of uncatalogued bat viruses and contributed to global surveillance efforts for emerging pathogens.[7] Shi Zhengli's work has drawn scrutiny amid hypotheses that SARS-CoV-2 originated from a laboratory incident at her institute, given the virus's emergence in Wuhan, the absence of identified animal intermediates despite extensive searches, and reports of respiratory illnesses among WIV researchers in autumn 2019.[8][9] Her team's experiments enhancing bat coronavirus pathogenicity, alongside documented biosafety concerns at the WIV's BSL-4 facility, have fueled arguments for a research-related accident over natural zoonosis, though she maintains no precursor viruses matching SARS-CoV-2 were held or leaked from her lab.[10][11][12]Biography
Early life and education
Shi Zhengli was born on May 26, 1964, in Xixia County, Henan Province, China.[13] [14] She received her Bachelor of Science degree in genetics from Wuhan University, completing her studies from September 1983 to June 1987.[15] Following this, Shi pursued graduate training at the Wuhan Institute of Virology under the Chinese Academy of Sciences, earning a Master of Science degree in virology between September 1987 and June 1990.[15] [16] In 1996, she began doctoral studies abroad, obtaining her PhD in virology from the University of Montpellier II in France in May 2000.[15] [16]Scientific Career
Establishment at Wuhan Institute of Virology
Shi Zhengli began her association with the Wuhan Institute of Virology (WIV) in 1987, immediately following her bachelor's degree from Wuhan University, when she enrolled for master's studies in virology at the institute under the Chinese Academy of Sciences.[17][16] She completed her master's degree there in 1990, focusing on viral pathogens, before pursuing a PhD at the University of Montpellier II in France from approximately 1990 to 1993.[16] Upon returning to China, Shi rejoined WIV as a research scientist in July 1993, a position she held until September 1995, conducting studies on viral diseases amid the institute's emphasis on emerging pathogens.[18] By July 2000, she had advanced to senior scientist at WIV, where she contributed to research on wildlife-borne viruses, including early investigations into bat reservoirs following the 2003 SARS outbreak.[18] Her work during this period laid the groundwork for specialized bat coronavirus studies, with her first field expedition for virus sampling occurring in 2004.[19] In 2010, WIV established a dedicated research center for emerging infectious diseases, aligning with national priorities for pathogen surveillance; Shi Zhengli was appointed director of this Center for Emerging Infectious Diseases, overseeing teams focused on zoonotic threats like bat coronaviruses.[20] Under her leadership, the center expanded virome discovery efforts, sequencing hundreds of novel viruses from bat populations across China and integrating high-containment facilities, including WIV's BSL-4 lab operationalized in 2018.[1] This progression solidified her role as a key figure in WIV's virology division, with her group amassing a repository of over 20,000 bat samples by the mid-2010s.[19]Research on bat coronaviruses and SARS origins
Shi Zhengli, a virologist at the Wuhan Institute of Virology, contributed to early investigations into the zoonotic origins of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) by focusing on bats as potential reservoirs. Following the outbreak, her team, in collaboration with researchers from the University of Hong Kong, screened anal swabs and feces from 408 bats across multiple provinces in China, identifying SARS-like coronaviruses (SL-CoVs) in 39 horseshoe bats (Rhinolophus spp.), with nucleotide identities up to 92% to the human SARS-CoV strain Tor2.[21] This 2005 study provided initial molecular evidence that bats, particularly Chinese horseshoe bats, serve as natural hosts for SARSr-CoVs, challenging prior assumptions centered on intermediate hosts like civets.[21] Building on this, Shi's group expanded field sampling in bat caves across Yunnan and other regions, emphasizing ecological surveys to trace viral diversity. In 2013, they reported the first isolation of a live SL-CoV, designated WIV1 (also Rs3367), from fecal samples of a Chinese horseshoe bat (Rhinolophus sinicus) in a Yunnan cave; pseudovirus assays confirmed its use of the human angiotensin-converting enzyme 2 (ACE2) receptor for entry, mirroring SARS-CoV's mechanism and suggesting potential for direct bat-to-human transmission without obligatory intermediates.[3] The isolated virus exhibited typical coronavirus morphology in Vero E6 cells and shared 96% genome identity with the civet SARS-CoV SZ3 strain, strengthening the case for bats as the primordial reservoir.[3][22] Subsequent work by Shi and colleagues further characterized bat-derived SARSr-CoVs for human infectivity potential. A 2015 study isolated and analyzed SHC014-CoV from horseshoe bats in Yunnan, constructing chimeric viruses by inserting its spike protein into a SARS-CoV backbone; these recombinants replicated in primary human airway cells and caused enhanced lung pathology in human ACE2-expressing mice compared to SARS-CoV controls, underscoring evolutionary risks from natural bat viruses.[6] In 2016, isolation of RsSHC014-CoV and related strains revealed genome sequences up to 96% identical to SARS-CoV, with spike proteins binding bat, civet, and human ACE2 receptors, indicating a broad host range in wild reservoirs.[23] By 2017, Shi's team had sequenced over 200 SARSr-CoVs from horseshoe bats in multiple Chinese provinces, uncovering a diverse gene pool including recombination hotspots in the receptor-binding domain; phylogenetic analyses traced the 2003 SARS-CoV spike to bat progenitors via recombination events, providing mechanistic insights into its emergence from wildlife.[7] These findings collectively established horseshoe bats as the likely origin of SARS-CoV through empirical isolation, sequencing, and functional testing, while highlighting ongoing spillover risks from uncultured bat viruses.[7]Key collaborations and publications pre-2020
Shi Zhengli's pre-2020 research emphasized field sampling of bats in Chinese caves and molecular characterization of SARS-like coronaviruses (SL-CoVs), often involving international partners for sequencing, receptor-binding assays, and functional studies. Her collaborations included long-term fieldwork and funding support from EcoHealth Alliance, led by Peter Daszak, which facilitated bat virus surveillance across China since at least 2004, yielding sequences for global databases.[24][14] These efforts identified diverse SL-CoVs in horseshoe bats (Rhinolophus spp.), with prevalence rates exceeding 10% in some Yunnan Province populations.[25] A pivotal partnership was with Ralph Baric's laboratory at the University of North Carolina, initiated around 2013, focusing on chimeric virus construction to assess cross-species transmission risks.[26] Shi's team supplied full-length SL-CoV genomes, such as SHC014 and WIV1, enabling Baric's group to create hybrids with SARS-CoV spike proteins; these experiments, funded partly by U.S. National Institutes of Health grants via EcoHealth, demonstrated infectivity in human airway cells and mice without adaptation.[6] Shi co-authored the resulting paper, which reported no severe disease in models but highlighted emergence potential.[6] Other collaborations spanned Australian virologists like Lin-Fa Wang for early bat sampling and European groups for phylogenetic analyses, contributing to over 100 SL-CoV sequences deposited pre-2020.[25] These works underscored bats as natural reservoirs but noted gaps in intermediate host identification.[27] Key pre-2020 publications by Shi include:| Year | Title | Journal | Key Details and Collaborators |
|---|---|---|---|
| 2005 | Bats are natural reservoirs of SARS-like coronaviruses | Nature | First isolation of SL-CoVs from Chinese horseshoe bats; collaborators included Wang LF (Australia). DOI: 10.1038/nature04188. |
| 2013 | Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor | Nature | Described WIV1-CoV binding human ACE2; Shi's team lead, with U.S. receptor experts. DOI: 10.1038/nature12711.[3] |
| 2015 | A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence | Nature Medicine | Chimeric SHC014-MA15 virus caused lung pathology in mice; co-authors Baric RS, Menachery VD; Shi provided bat sequences. DOI: 10.1038/nm.3985.[6] |
| 2018 | Origin and evolution of pathogenic coronaviruses | Nature Reviews Microbiology | Review of bat origins for SARS/MERS; co-authors Cui J, Li F. DOI: 10.1038/s41579-018-0118-9.[25] |