Wei-Shau Hu, Ph.D.
Wei-Shau Hu, Ph.D.
Dr. Hu is widely recognized as a key authority on retroviral recombination, RNA packaging, and virus assembly. Her innovations in combining molecular biology and biochemical approaches with state-of-the-art microscopy techniques for single-virion particle analysis have led to significant advancements in HIV molecular virology research. Under Dr. Hu’s direction, the Viral Recombination Section investigates multiple aspects of the retroviral life cycle that affect the transfer of viral genetic information. These studies have profound implications for questions that are fundamentally important to HIV replication, which can be used to generate new strategies to block the spread of HIV.
1) HIV pathogenesis, 2) retroviral replication, 3) RNA packaging and virus assembly, 4) virology, 5) molecular biology, 6) infectious diseases
Retroviral RNA Trafficking, RNA Packaging, Virus Assembly, and Replication
We study how retroviruses transfer genetic information to the next generation. HIV-1 packages two copies of full-length viral RNA into a particle. Upon infecting a new host cell, virion RNA is used as the template to generate viral DNA, which integrates into the host chromosome to form a provirus. We study several aspects of the viral replication cycles that affect the transfer of viral genetic information, including the transport and trafficking of the viral RNA, packaging of the viral RNA genome, virus assembly, and reverse transcription. We use molecular biology and biochemical approaches in combination with state-of-the-art microscopy techniques to study these topics.
Retroviral RNA packaging and virus assembly. In order to generate infectious viruses, HIV-1 must encapsidate full-length unspliced RNAs into its particle. To study HIV-1 RNA packaging, we have developed a novel assay to directly visualize viral RNA in the particles at single-RNA-molecule sensitivity. This assay reveals that most HIV-1 particles contain two copies of full-length viral RNA. Although it is known that retroviral RNAs that are packaged into particles are dimeric, standard biochemical assays cannot determine the number of RNA molecules in one particle; our results provide evidence to support the long-standing assumption that two RNA molecules (one dimer) are packaged into a particle. To better understand the mechanisms of RNA packaging, we have performed genetic, biochemical, and imaging analyses to show that HIV-1 RNA uses base-pairing of the dimerization initiation signal sequence to select its copackaged RNA partner, and this process occurs in the cytoplasm of the producer cell prior to RNA packaging into particles. We study the mechanisms that HIV-1 uses to regulate which and how many RNAs are packaged. Additionally, we study the interactions between viral Gag protein and full-length RNA that lead to the encapsidation of the viral genome during virus assembly.
Retroviral RNA trafficking. Full-length HIV-1 RNA needs to traffic to specific subcellular locations to carry out its functions, including serving as a template for Gag/Gag-Pol translation and as a genome in the newly assembled virion. The functions of the viral RNA and the translated proteins can be affected when RNA is targeted to incorrect locations in the cells. Using our newly developed imaging tools and live-cell imaging techniques, we study HIV-1 RNA transport and its relation to the function of viral RNAs. These experiments will provide an understanding of aspects of HIV-1 replication that we currently know very little about and will allow us to better understand how HIV-1 uses the cellular machinery to traffic its macromolecules.
Reverse transcription and recombination. Recombination plays an important role in HIV replication and evolution. For example, many of the primary isolates of HIV are recombinants, and recombination can assort mutations to generate variants that escape host immune responses or are resistant to multidrug treatment protocols. Recombination of HIV-1 occurs during reverse transcription, using information in the two RNAs to produce a hybrid DNA. Therefore, phenotypically different recombinants are generated from viruses containing two copies of different RNAs. Only cells that are doubly infected can produce virions containing two different RNAs. To better understand interactions in HIV-1 populations, we study the dynamics of double infection, the frequency of recombination, and the mechanism of reverse transcription.
Selected Key Publications
- Proc Natl Acad Sci U S A. 117: 6145-6155, 2020. [ Journal Article ]
Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity.Nucleic Acids Res. 46: 10535-10545, 2018. [ Journal Article ]
- Proc Natl Acad Sci U S A. 113: E201-E208, 2016. [ Journal Article ]
- Proc Natl Acad Sci U S A. 111: E5205-E5213, 2014. [ Journal Article ]
- PLoS Pathog. 9(3): e1003249, 2013. [ Journal Article ]
Dr. Wei-Shau Hu received her Ph.D. in Genetics from the University of California, Davis, in 1987. She studied the mechanisms of DNA recombination that lead to human alpha-thalassemia in Dr. James Shen's laboratory. Under Dr. Howard Temin's guidance, she studied the mechanisms of retroviral recombination as a postdoctoral fellow at the University of Wisconsin. In 1991, Dr. Hu joined the faculty of West Virginia University as an Assistant Professor in the Department of Microbiology and Immunobiology and the Mary Babb Randolph Cancer Center. She was promoted to Associate Professor with tenure in 1998. In 1999, she joined the National Cancer Institute (NCI) as Senior Investigator and Head of the Viral Recombination Section in the HIV Drug Resistance Program (renamed the HIV Dynamics and Replication Program in 2015). Dr. Hu was an organizer of the 2009 Cold Spring Harbor Retroviruses conference. She served as the Frederick representative of Women Science Advisors for the NCI from 2012 to 2016 and as a member of the AIDS Molecular and Cellular Biology Study Section of the National Institutes of Health extramural grant funding programs from 2010 to 2016. In 2012, she was the recipient of one of the five grants that the U.S.-Russia Joint Working Group on Biomedical Research Cooperation awarded to NCI intramural investigators for their highly meritorious research applications; Dr. Hu's application was focused on understanding the impact of HIV-1 recombination and cell-to-cell transmission on vaccine development and chemoprevention strategy. In 2021, she was elected as a Fellow in the American Society of Microbiology and was selected by the Center for Retrovirus Research of The Ohio State University to receive the 2021 Distinguished Research Career Award. Dr. Hu currently serves as a member of the HIV Interactions in Viral Evolution (HIVE) Center, NCI Promotion Review Panel, and NCI RNA Biology Initiative.
|Position||Degree Required||Contact Name||E-mail Address|
|Post-doctoral Fellow - HIV replication, retroviral RNA packaging||Ph.D. or equivalent, M.D. or equivalent||Wei-Shau Hu, Ph.D.||email@example.com|
|Matthew Brown||Postbaccalaureate Fellow (CRTA)|
|Jianbo Chen, Ph.D.||Staff Scientist|
|Zetao Cheng Ph.D.||Postdoctoral Fellow (Visiting)|
|Alice Duchon Ph.D.||Postdoctoral Fellow (CRTA)|
|Mohammad Saiful Islam Ph.D.||Postdoctoral Fellow (Visiting)|
|Olga A. Nikolaitchik Ph.D.||Research Biologist|
|Jonathan Rawson Ph.D.||Research Fellow|
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Undergraduate Student, University of Maryland, College Park, MD
M.D. Student, University of Oklahoma College of Medicine, Oklahoma City, OK
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Associate Professor, National Institute of Health, and University of Osaka, Osaka, Japan
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Senior Technology Development Program Assistant, Optum, Basking Ridge, NJ
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Researcher, FDA Center for Biologics Evaluation and Research, Rockville, MD
Teaching Assistant, University of Maryland, College Park, MD
Postdoctoral Fellow, Emory University, Atlanta, GA
Associate Professor, University of Washington School of Medicine, and Surgical Director of Liver Transplant, Seattle Children’s Hospital, Seattle, WA
Clinical Assistant Professor of Medicine, West Virginia University, Charleston, WV
Scientific Review Officer, National Institute of Allergy and Infectious Diseases, Bethesda, MD
Senior Scientist, Infectious Disease and Vaccines – HIV Discovery, Merck, West Point, PA
Postdoctoral Fellow, Laboratory of Cell and Developmental Signaling, National Cancer Institute, Frederick, MD
Ph.D. Student, Microbiology and Immunology, University of Pittsburgh, Pittsburgh, PA
Simon Fraser University, British Columbia, Canada
Research Scientist, NDLOVU Care Group, South Africa, and Founder, Water at Home
Neurosurgical Physician Assistant, West Virginia University, Morgantown, MD
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Wei-Shau Hu Selected to Receive 2021 Distinguished Research Career Award from The Ohio State University Center for Retrovirus Research
Wei-Shau Hu was selected by the Center for Retrovirus Research (CRR) of The Ohio State University to receive the 2021 Distinguished Research Career Award. This annual award honors the distinguished research career of a scientist working in the field of retrovirology. The retrovirologist is nominated by student and faculty members of the CRR and as part of the award recognition is invited to give a special lecture to all members of The Ohio State University biomedical research community, co-sponsored by the CRR, the Infectious Diseases Institute, the Comprehensive Cancer Center, and the campus-wide Virology Forum. Dr. Hu will receive the award and present her honorary lecture in the fall 2021.
NIH Fellows Awards for Research Excellence
Jonathan Rawson received a 2021 NIH Fellows Award for Research Excellence (FARE) for travel to attend and present his work at a scientific meeting in the U.S. This award, which acknowledges outstanding scientific research performed by intramural postdoctoral fellows, is sponsored by the NIH Fellows Committee, Scientific Directors, and Office of Intramural Training and Education and is funded by the Scientific Directors. FARE awards are based on scientific merit, originality, experimental design, and overall quality and presentation of the abstracts.
Members of the Hu Lab who were FARE awardees in previous years include Alice Duchon and Chijioke Umunnakwe (2020), Jonathan Rawson (2019), Sheikh Abdul Rahman (2016), Luca Sardo (2015), Kari Dilley (2012), Michael Moore (2009), Mario P.-S. Chin (2006 and 2007), Kazushi Motomura (2007), and Olga Nikolaitchik (2006).
Wei-Shau Hu Elected to American Academy of Microbiology
Wei-Shau Hu was elected as a Fellow in the American Society of Microbiology (AAM) in February 2021. The AAM is the honorific leadership group within the American Society for Microbiology, the world’s largest society dedicated to advancing the microbial sciences. AAM Fellows are recognized as distinguished researchers who are "elected through a highly selective, annual, peer review process, based on their records of scientific achievement and original contributions that have advanced microbiology....Each elected Fellow has built an exemplary career in basic and applied research, teaching, clinical and public health, industry or government service."
PNAS Cozzarelli Prize Awarded to Pathak and Hu Labs
A recent study published by the research groups of Vinay Pathak and Wei-Shau Hu in Proceedings of the National Academy of Sciences USA (“HIV-1 uncoats in the nucleus near sites of integration,” PNAS 117: 5486-5493, 2020) was awarded the 2020 Cozzarelli Prize in the class of Biomedical Sciences. The Cozzarelli Prize is awarded to just 6 papers chosen from nearly 4,000 published research articles, one in each of the 6 classes of the National Academy of Sciences. They represent the top scientific research published in PNAS in 2020. To read more about this award, click here.
Uncoating of an infectious HIV-1 complex is shown at left. Click on the figure for a full caption and here to download the original video (Movie S1 in the paper).
[This study was also featured on the website of the Center for Cancer Research, National Cancer Institute (“New study overturns conventional understanding of how HIV infection occurs”) and highlighted on the front cover of the Cold Spring Harbor 2020 Retroviruses Meeting abstract book (read more).]
Research by Pathak and Hu Labs Featured on Cover of 2020 Retroviruses Meeting Abstract Book
A recent study published by the research groups of Vinay Pathak and Wei-Shau Hu in Proceedings of the National Academy of Sciences USA (“HIV-1 uncoats in the nucleus near sites of integration,” PNAS 117:5486-5493, 2020) was featured on the front cover of the Cold Spring Harbor 2020 Retroviruses Meeting abstract book. Pathak lab member Ryan Burdick launched the meeting with his talk on the study and reported that HIV-1 uncoats in the nucleus near sites of integration. Contrary to the prevailing theory for more than 40 years that retroviral uncoating occurs in the cytoplasm, the study team showed that HIV-1 cores are essentially intact as they enter the nucleus, where they complete reverse transcription before uncoating near their sites of integration into the host genome. These unexpected results fundamentally alter the current understanding of HIV-1 replication, which could lead to the development of more effective strategies and drugs for the treatment of HIV infections.
In the cover image, the left panel shows an HIV-1 capsid localized in the nucleus and the right panel shows a site of transcription of the viral genome at the site where the capsid localized. To read more about the study, see the original research article and the commentary "Entering and breaking for HIV?" in Nature Reviews Microbiology.
[This study was also awarded the 2020 PNAS Cozzarelli Prize and featured on the website of the Center for Cancer Research, National Cancer Institute (“New study overturns conventional understanding of how HIV infection occurs”).]
CCR News Feature about HIV-1 Infection Study by Pathak and Hu Labs
New Study Overturns Conventional Understanding of How HIV Infection Occurs
With unprecedented detail, researchers have observed where and when the protective casing around the human immunodeficiency virus (HIV-1) is shed inside a human cell, which is an observation that overturns the conventional understanding of how the virus infects cells and replicates. The finding was published February 24, 2020, in the Proceedings of the National Academy of Sciences (PNAS) USA.
“Understanding how HIV-1 replication occurs can provide valuable insights into essential interactions between the virus and the host cell,” explains Vinay K. Pathak, Ph.D., Senior Investigator in the Retroviral Replication Laboratory, part of the HIV Dynamics and Replication Program.
Despite the importance of understanding how the virus infects human cells, many details about this process have remained unknown. Until now, many scientists suspected that the protective casing around the virus, called the viral capsid, was shed before the virus enters the center of a human cell, called the nucleus. Once inside the nucleus, the virus begins to replicate itself.
Pathak’s lab used a new approach to brightly label the viral capsid with fluorescence in order to track it. Previous efforts to label the viral capsid with fluorescent proteins resulted in dimly labeled or defective viruses, making it difficult to study the uncoating process.
Unexpectedly, they found that the viral capsid remained essentially intact after entering the nuclei of cells. They also identified a key protein called CPSF6 that helps facilitate the transport of the virus, including its capsid, through the pores of a nucleus.
“We hope that the insights gained in our studies will help to identify critical molecular interactions between the virus and the host that will facilitate the development of new classes of potent anti-retroviral drugs,” says Pathak.
However, he notes, this study raises many unanswered questions. It’s still a mystery, for example, on how the full virus (capsid included) at a diameter of roughly 61 nanometers can squeeze through the pore of a human nucleus, which is only about 39 nanometers wide. More research is needed to understand how this happens and to identify the mechanisms that help trigger the virus’s uncoating process.
Confocal image of an infected cell nucleus (purple) shows an HIV-1 capsid core (green spot, left panel) just before uncoating and a transcriptionally active provirus (bright purple spot, right panel) that appears several hours later near the site of uncoating. Image credit: Ryan C. Burdick.
[This study was also awarded the 2020 PNAS Cozzarelli Prize and highlighted on the front cover of the Cold Spring Harbor 2020 Retroviruses Meeting abstract book (read more).]
New Investigator Scholarships, Conference on Retroviruses and Opportunistic Infections
Alice Duchon and Jonathan Rawson were awarded New Investigator Scholarships in 2020 to present their research findings in the Conference on Retroviruses and Opportunistic Infections (CROI). CROI scholarship awardees in previous years include Chijioke (CJ) Umunnakwe (2019), Yang Liu (2017), and Luca Sardo (2015).
Intramural AIDS Research Fellowship Awards
Intramural AIDS Research Fellowship (IARF) awards from the Office of AIDS Research, Office of Intramural Research, and Office of Intramural Research & Training in the National Institutes of Health include full stipend support to successful candidates who demonstrate outstanding scientific potential through both an imaginative and thoughtful research plan and a well thought out career development plan.
Alice Duchon received an IARF Award in 2019 and 2020 to support her research project on "Understanding the Interplay between HIV-1 Gag and the Viral RNA Genome that Facilitates Virus Assembly." Jonathan Rawson received an IARF Award in 2017 and 2018 to support his research project on "Understanding the Pseudodiploid Nature of HIV-1."
>NIH Summer Mentor Award
Jonathan Rawson received a 2018 NIH Summer Mentor Award. The NIH Summer Mentor Award Program provides for a centrally funded summer intern to train with qualified postdoctoral fellows, visiting fellows, clinical fellows, and graduate students. Dr. Rawson's trainee is Franck Mbuntcha Bogni, a student who is participating in the NIH Community College Summer Enrichment Program this year.
Travel Award, HIV DRP Think Tank Meeting
Yang Liu received a travel award for one of the two best presentations by NCI fellows at the 2015 HIV DRP Think Tank Meeting. The $1000 travel award was provided by the HIV DRP, Center for Cancer Research, NCI.
Award from U.S.-Russia Joint Working Group on Biomedical Research Cooperation
In 2012, Wei-Shau Hu was the recipient of one of the five grants that the U.S.-Russia Joint Working Group on Biomedical Research Cooperation awarded to National Cancer Institute intramural investigators for their highly meritorious research applications. Dr. Hu is the Principal Investigator on a project focused on understanding the impact of HIV-1 recombination and cell-to-cell transmission on vaccine development and chemoprevention strategy.
Marie Curie Postdoctoral Fellowship
Andrea Galli was awarded a Marie Curie Postdoctoral Fellowship in 2011 by Copenhagen University.
Howard Temin Pathway to Independence Award (K99/R00)
In 2008, Mario P.-S. Chin successfully competed for a Howard Temin Pathway to Independence (PI) Award (K99/R00) from the National Institutes of Health. The PI Award Program establishes and maintains a strong cohort of new and talented NIH-supported independent investigators. Subsequent to receiving this award, Dr. Chin accepted a position at the Aaron Diamond AIDS Research Center (ADARC) in New York as the first ADARC Scholar. At the ADARC, he has established an independent research program that is focused on the evolution and adaption of HIV-1 in response to antiviral drug and host immune selection pressures.
Kitazato Shibasaburo Award
In 2008, Kazushi Motomura won the Kitazato Shibasaburo Award in recognition of the important findings from a study on HIV-1 and HIV-2 recombination that he reported with Jianbo Chen and Wei-Shau Hu (J. Virol. 82: 1923-1933, 2008). This award is one of the most prestigious prizes in the infectious disease field in Japan.
Scholarship Award, Keystone Symposia on HIV Pathogenesis
Michael Moore was awarded a travel scholarship to present his research findings at the 2008 Keystone Symposia on HIV Pathogenesis.
Scholarship Award, International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
Mario P.-S. Chin was awarded a scholarship to present his findings at the 2007 IAS Conference on HIV Pathogenesis, Treatment and Prevention in Sydney, Australia.
Poster Awards, Spring Research Festival at NCI-Frederick
Michael Moore and Olga Nikolaitchik won poster awards for their presentations at the NCI-Frederick Spring Research Festival in 2007 and 2006, respectively.