10th Annual David Derse Memorial Lecture and Award: Akiko Iwasaki
The 10th Annual David Derse Memorial Lecture and Award presentation will be held virtually on November 16, 2021. This annual event honors the outstanding research accomplishments of David Derse, Ph.D., Principal Investigator and Head of the Retrovirus Gene Expression Section in the HIV DRP. During his 25 years at the National Cancer Institute, Dr. Derse investigated the molecular mechanisms of retrovirus infection and replication, concentrating most recently on the human viruses HIV-1 and HTLV-1. In 2007, he and his research team discovered how HTLV-1 evades the body's natural defenses to fight off infection, a finding that may eventually lead to improved antiviral therapies and new strategies for preventing some types of cancer.
The HIV DRP sponsors the Annual David Derse Memorial Lecture and Award, with support from Hye Kyung Chung-Derse and the National Cancer Institute, to foster the scientific discourse and exchange of innovative ideas that Dr. Derse was well known for promoting throughout his scientific career.
Akiko Iwasaki, Ph.D. (Waldemar Von Zedtwitz Professor of Immunology and Molecular, Cellular and Developmental Biology at Yale University School of Medicine and Howard Hughes Medical Institute Investigator) will deliver the tenth lecture in this series. The title of her presentation is “Immune Responses to SARS-CoV-2.”
Additional details, including the agenda and information about joining the virtual event by Webex, are available at https://ncifrederick.cancer.gov/events/conferences/tenth-annual-david-derse-memorial-lecture-and-award-2021. After the event, an archived videocast will be available for viewing at videocast.nih.gov/watch=43976.
2021 HIV DRP Conference on Virus Entry and Post-Entry Events
Virus Entry and Post-Entry Events was held on October 13, 2021. The HIV DRP organized this virtual conference to showcase the latest research on the cell, molecular, and structural biology of virus entry and post-entry, focusing on new approaches to understanding the mechanisms of viral pathogenesis with the goal of developing improved therapeutics against existing and emerging infectious diseases, including COVID-19. Invited speakers in this outstanding program included Sarah Butcher, Daniel DiMaio, Ekaterina Heldwein, Wendy Maury, Walther Mothes, Vinay Pathak, Stefan Pöhlmann, Félix Rey, and Erica Ollmann Saphire. After the conference, an archived videocast will be available for viewing at https://videocast.nih.gov/watch=43962. Additional details, including the conference agenda, are available at https://ncifrederick.cancer.gov/events/conferences/virus-entry-and-post-entry-events.
In previous years, the HIV DRP Conference showcased other topics on the discovery, development, and delivery of antiviral and immunologic approaches for the prevention and treatment of viral infection, including Virus-Cell Interactions: New Approaches and Technologies; Therapeutic Interventions and Resistance Mechanisms; Establishment and Control of Viral Persistence; Innate Immunity: Sensing, Signaling, and Selection; Emerging Viruses: Origins, Biology, and Control of Transmission; Approaches to a Functional Cure for HIV Infection; Virus Structure: Putting the Pieces Together; Host Factors and Cofactors in HIV Infection; and Trafficking of Viral Macromolecules.
Wei-Shau Hu and Mary Kearney Appointed as Deputy Directors in HIV Dynamics and Replication Program
In October 2021, Wei-Shau Hu and Mary Kearney were appointed as Deputy Director of Basic Research and Deputy Director of Translational/Clinical Research, respectively, in the HIV Dynamics and Replication Program.
Vinay Pathak Discussed HIV-1 Uncoating Discovery on PNAS Science Sessions Podcast
In a June 2021 interview on Science Sessions, the podcast program of the Proceedings of the National Academy of Sciences USA (PNAS), Vinay Pathak explained the story behind the HIV-1 uncoating discovery by his lab in collaboration with Wei-Shau Hu's research team, a groundbreaking advance that was awarded the 2020 PNAS Cozzarelli Prize in Biomedical Sciences. To listen to the podcast, click here.
PNAS Video on Cozzarelli Prize Awarded to Pathak and Hu Labs
In a video produced by Proceedings of the National Academy of Sciences USA (PNAS) about the 2020 Cozzarelli Prize in Biomedical Sciences, Vinay Pathak discusses the HIV-1 uncoating discovery by his research team in collaboration with Wei-Shau Hu's lab. The video can be viewed on the PNAS Cozzarelli Prize page and on the PNAS YouTube channel (click here).
The publication that Dr. Pathak discusses in the video (“HIV-1 uncoats in the nucleus near sites of integration,” PNAS 117:5486-5493, 2020) 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.
Podcast Featured Vinay Pathak Discussing Live-Cell Imaging of HIV-1
Vinay Pathak was interviewed in a podcast by Consultant360 Specialty Network on the research presented in the "Navigating to the Nucleus" session at the Conference on Retroviruses and Opportunistic Infections 2021, including his presentation on "Live-Cell Imaging of HIV-1 Nuclear Import, Uncoating, and Proviruses." To listen to the podcast, click here.
9th Annual David Derse Memorial Lecture and Award: Stephen P. Goff
The 9th Annual David Derse Memorial Lecture and Award presentation was held virtually on November 10, 2020. This annual event honors the outstanding research accomplishments of David Derse, Ph.D., Principal Investigator and Head of the Retrovirus Gene Expression Section in the HIV DRP. During his 25 years at the National Cancer Institute, Dr. Derse investigated the molecular mechanisms of retrovirus infection and replication, concentrating most recently on the human viruses HIV-1 and HTLV-1. In 2007, he and his research team discovered how HTLV-1 evades the body's natural defenses to fight off infection, a finding that may eventually lead to improved antiviral therapies and new strategies for preventing some types of cancer.
The HIV DRP sponsors the Annual David Derse Memorial Lecture and Award, with support from Hye Kyung Chung-Derse and the National Cancer Institute, to foster the scientific discourse and exchange of innovative ideas that Dr. Derse was well known for promoting throughout his scientific career.
Stephen P. Goff, Ph.D. (Higgins Professor of Biochemistry and Molecular Biophysics at Columbia University Medical Center and Howard Hughes Medical Institute Investigator) delivered the ninth lecture in this series. The title of his presentation was “Silencing of Retroviral DNAs.”
The archived videocast of this event is available on the NIH Videocast website at videocast.nih.gov/watch=40067.
2020 HIV DRP Conference on Virus-Cell Interactions: New Approaches and Technologies
Virus-Cell Interactions: New Approaches and Technologies was held on October 21, 2020. The HIV DRP organized this virtual conference to showcase the latest research on virus–cell interactions, focusing on new approaches to understanding the mechanisms of viral pathogenesis and host antiviral defenses, with the goal of developing improved therapeutics against existing and emerging infectious diseases.
Invited speakers in the outstanding program included Stephen Elledge (Harvard Medical School and Howard Hughes Medical Institute), Timothy Henrich (University of California San Francisco), Christopher Hill (University of Utah School of Medicine), Judd Hultquist (Northwestern University), Taina Immonen (National Cancer Institute-Frederick), Daniel Kaufmann (University of Montreal), James Munro (University of Massachusetts Medical School), Tatyana Polenova (University of Delaware), and Elizabeth Wright (University of Wisconsin-Madison).
In previous years, the HIV DRP Conference showcased other topics on the discovery, development, and delivery of antiviral and immunologic approaches for the prevention and treatment of viral infection, including Therapeutic Interventions and Resistance Mechanisms; Establishment and Control of Viral Persistence; Innate Immunity: Sensing, Signaling, and Selection; Emerging Viruses: Origins, Biology, and Control of Transmission; Approaches to a Functional Cure for HIV Infection; Virus Structure: Putting the Pieces Together; Host Factors and Cofactors in HIV Infection; and Trafficking of Viral Macromolecules.
Stephen Hughes: Inside the War Room Against Drug-Resistant HIV
[The following excerpt is from the article "Inside the War Room Against Drug-Resistant HIV," published by Samuel Lopez in the NCI at Frederick Poster, 8 September 2020.]
Steve Hughes, Ph.D., compares HIV research to a war. He and his colleagues are entrenched on a microscopic battlefield, fighting a conflict where seemingly small victories could mean a leap forward.
Right now, they are grappling with the emergence of HIV strains resistant to existing antiretroviral drugs, medicines that suppress the virus in people living with HIV. The team’s current target is integrase, an enzyme that HIV uses to insert a DNA copy of its genetic information into the DNA of a host cell, thereby allowing the virus to replicate and spread.
HIV research and treatment have come far in the four decades since the virus was discovered. Today, most infections can be managed by therapies that use a combination of state-of-the-art antiretroviral drugs. But mutated strains that resist even the best HIV drugs can arise. Developing treatments for them is an ongoing battle in a long war.
“There are some mutants that are a problem, and the ones that are really bad are a problem for everybody,” said Hughes, chief of the Retroviral Replication Laboratory and senior investigator in the HIV Dynamics and Replication Program at NCI at Frederick.
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 in Biomedical Sciences and featured on the website of the Center for Cancer Research, National Cancer Institute (“New study overturns conventional understanding of how HIV infection occurs”).
In Memoriam: Stephen Oroszlan, Ph.D., Scientist Emeritus
The HIV DRP mourns the recent death of Stephen Oroszlan, a pioneer in studies related to the biochemistry and enzymology of retroviral replication and the biosynthesis of retroviral enzymes and structural proteins.
Dr. Oroszlan received his early training in chemical engineering in his native Hungary. Following his immigration to the U.S., he obtained a Ph.D. in Pharmacology from Georgetown University. After his postdoctoral training at the NCI from 1961 to 1963, he conducted biochemistry research on retroviruses at the Albert Einstein Medical Center, George Washington University School of Medicine, and Flow Laboratories. In 1976 he returned to the NCI and served as Director of the Molecular Virology and Carcinogenesis Laboratory, ABL-Basic Research Program, from 1983 to 1995. He was appointed Scientist Emeritus in 1995, and since 1999 he had been affiliated with the HIV DRP.
Dr. Oroszlan was perhaps best known for his groundbreaking research defining the role of retroviral proteases in the generation of mature Gag-related protein products, which comprise the virus particle structure. This work played a central role in the development of HIV protease inhibitors, which became a mainstay in the treatment of HIV-infected individuals. His laboratory also discovered that many retroviral Gag proteins are modified with the fatty acid myristate, a finding that was of great importance in understanding the assembly of retroviral particles. He published more than 250 papers and was named one of the most highly cited researchers in microbiology by the Institute for Scientific Information.
Dr. Oroszlan's numerous honors include the award of a Doctor Honoris Causa Degree from the University of Debrecen Medical School in 1993, election to the Hungarian Academy of Sciences as a foreign associate in 1994, a Retroviral Retrospective Symposium held in his honor at Hood College in 1994, and the Mór Kaposi Research Foundation Award in 2000.
Alan Rein, a longtime colleague of Dr. Oroszlan’s and head of the Retrovirus Assembly Section in the HIV DRP, is serving as a guest editor for the Viruses Special Issue “In Memory of Stephen Oroszlan” to honor his work and scientific legacy.
CCR News Feature about HIV-1 Infection Study by Pathak and Hu Labs
[Excerpted from a 26 February 2020 news feature by Center for Cancer Research (CCR), National Cancer Institute]
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 in Biomedical Sciences and highlighted on the front cover of the Cold Spring Harbor 2020 Retroviruses Meeting abstract book.]