Wesley Sundquist

Last updated

Wesley I. Sundquist (born 1959) is an American biochemist. Sundquist is known for studying the cellular, molecular and structural biology of retroviruses, particularly HIV. He is also known for studying the ESCRT pathway in cell division. [1]

Contents

Wesley I. Sundquist Wes Sundquist.pdf
Wesley I. Sundquist

Wesley Sundquist was born in St. Paul, Minnesota in 1959. He grew up in St. Paul Minnesota and Washington, DC. He received his bachelor’s degree in Chemistry from Carleton College in Minnesota in 1981. During his time at Carleton Sundquist served as the coordinator of the Faribault Project, was elected to Sigma Xi and received a National Merit Scholarship (1977-81). Sundquist went on to complete a PhD at the Massachusetts Institute of Technology with Stephen J. Lippard in 1988. Following his PhD, he participated in postdoctoral research at the MRC Laboratory of Molecular in Cambridge, England under Sir Aaron Klug. In 1992 Sundquist joined the University of Utah Department of Biochemistry. [2] Sundquist is married to Nola Sundquist, with whom he lives with in Salt Lake City, Utah. They have two adult children, Chris and Emily.

Work and discoveries

HIV Budding Hiv budding.jpg
HIV Budding

Sundquist is Distinguished Professor and Chair of the Department of Biochemistry at the University of Utah, and he also directs a research lab. The Sundquist Lab focuses on cellular, molecular and structural biology of retroviruses with a focus on Human Immunodeficiency Virus, HIV. Major projects in his lab include, 1) enveloped virus assembly 2) ESCRT pathway functions and regulation in cell division and cancer, and 3) HIV capsid structure, replication and restriction. [3]

Enveloped virus assembly and budding

To leave a cell and spread infection, HIV viral particles must become enveloped within a membrane and bud from the cell. Sundquist found that retroviruses like HIV bud from infected cells using the host Endosomal Sorting Pathway Required for Transport or ESCRT pathway. HIV also uses the host proteins of the Angiomotin family to facilitate membrane envelopment prior to ESCRT- mediated budding. Sundquist's current research in this area focuses on understanding assembly and budding of HIV, characterizing the host and viral proteins involved, and testing innate immune restriction of viruses that use the ESCRT pathway. The Sundquist lab has also used their understanding of the requirements and principles of enveloped virus assembly to design and characterize new proteins that can assemble into nanocages, bud from cells, and carry cargoes into new target cells.

Selected publications

  • von Schwedler U, Stuchell M, Müller B, Ward D, Chung H-Y, Morita E, Wang H, Davis T, Gong-Ping H, Cimbora DM, Scott AT, Kräusslich H-G, Kaplan J, Morham SG, and Sundquist WI. (2003). The protein network of HIV budding. Cell, 114, 701-713.

ESCRT pathway functions and cell division

Asymmetric ring structure of Vps4 required for ESCRT III disassembly Asymmetric ring structure of the Vps4-Vta1 complex required for ESCRT-III remodeling.pdf
Asymmetric ring structure of Vps4 required for ESCRT III disassembly

The ESCRT pathway facilitates formation of vesicles that bud into the endosome, neuronal pruning, reassembly of the post-mitotic nuclear envelope, final stage cell division (cytokinetic abscission). Cytokinetic abscission completes the separation of the two daughter cells, and also helps to coordinate a checkpoint that delays cell division until mitotic processes are completed successfully. In some cancer cells, this regulation doesn’t function correctly. Sundquist’s lab is studying these processes by determining the structures and functions of individual ESCRT proteins and the cofactors they recruit to help mediate abscission and the abscission checkpoint, and the signaling pathways that control their activities.

Selected publications

HIV replication and restriction

HIV virion structure HI-virion-structure en.svg
HIV virion structure

The capsid of HIV facilitates viral reverse transcription and protects the viral genome from the innate immune system. Sundquist defined the fullerene cone structure of the viral capsid, helping to set the stage for development of highly potent and long-lasting capsid inhibitors at Gilead Sciences. The Sundquist lab was also the first to reconstitute HIV reverse transcription and integration in a cell-free system. Sundquist and his collaborators also helped to define how the host restriction factor, TRIM5alpha recognizes and assembles around the capsid.

Selected publications

Honors and scientific legacy

In 1993 Sundquist received the Searle Scholars Award.

In 2003 he received the ASBMB Amgen Award for the Application of Biochemistry and Molecular Biology to the understanding of disease.

In 2004 he received both the MERIT award from the National Institutes of Health and the Bernard Fields award for Retrovirology.

In 2017 he received the University of Utah Rosenblatt Prize for Excellence.

He has been elected to the American Academy of Arts and Sciences (2011) and the National Academy of Sciences. [2] (2014).

Related Research Articles

<span class="mw-page-title-main">TRIM5alpha</span>

Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the TRIM5 gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates a species-specific early block to retrovirus infection.

<span class="mw-page-title-main">Viral protein</span>

A viral protein is both a component and a product of a virus. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, nonstructural proteins, regulatory proteins, and accessory proteins. Viruses are non-living and do not have the means to reproduce on their own, instead depending on their host cell's resources in order to reproduce. Thus, viruses do not code for many of their own viral proteins, and instead use the host cell's machinery to produce the viral proteins they require for replication.

Viral matrix proteins are structural proteins linking the viral envelope with the virus core. They play a crucial role in virus assembly, and interact with the RNP complex as well as with the viral membrane. They are found in many enveloped viruses including paramyxoviruses, orthomyxoviruses, herpesviruses, retroviruses, filoviruses and other groups.

Rous sarcoma virus (RSV) is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in chickens.

<span class="mw-page-title-main">Viral envelope</span> Outermost layer of many types of the infectious agent

A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes.

Simian foamy virus (SFV) is a species of the genus Spumavirus that belongs to the family of Retroviridae. It has been identified in a wide variety of primates, including prosimians, New World and Old World monkeys, as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV, including African green monkeys, baboons, macaques, and chimpanzees. As it is related to the more well-known retrovirus human immunodeficiency virus (HIV), its discovery in primates has led to some speculation that HIV may have been spread to the human species in Africa through contact with blood from apes, monkeys, and other primates, most likely through bushmeat-hunting practices.

Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus. It was named as such because scientists used to believe it was antigenic. Now it is known that it makes up the inner shell, not the envelope exposed outside. It makes up all the structural units of viral conformation and provides supportive framework for mature virion.

The gag-onc fusion protein is a general term for a fusion protein formed from a group-specific antigen ('gag') gene and that of an oncogene ('onc'), a gene that plays a role in the development of a cancer. The name is also written as Gag-v-Onc, with "v" indicating that the Onc sequence resides in a viral genome. Onc is a generic placeholder for a given specific oncogene, such as C-jun..

<span class="mw-page-title-main">TSG101</span>

Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.

<span class="mw-page-title-main">Viral shedding</span> Dissemination of mature virions from host cell

Viral shedding is the expulsion and release of virus progeny following successful reproduction during a host cell infection. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.

<span class="mw-page-title-main">PDCD6IP</span>

Programmed cell death 6-interacting protein also known as ALIX is a protein that in humans is encoded by the PDCD6IP gene.

<span class="mw-page-title-main">VPS24</span>

Charged multivesicular body protein 3 is a protein that in humans is encoded by the VPS24 gene.

<span class="mw-page-title-main">VPS4A</span> Protein-coding gene in the species Homo sapiens

Vacuolar protein sorting-associated protein 4A is a protein that in humans is encoded by the VPS4A gene.

<span class="mw-page-title-main">VPS28</span> Protein-coding gene in the species Homo sapiens

Vacuolar protein sorting-associated protein 28 homolog is a protein that in humans is encoded by the VPS28 gene.

<span class="mw-page-title-main">CHMP5</span> Protein-coding gene in the species Homo sapiens

Charged multivesicular body protein 5 is a protein that in humans is encoded by the CHMP5 gene.

The endosomal sorting complexes required for transport (ESCRT) machinery is made up of cytosolic protein complexes, known as ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes bending/budding away from the cytoplasm. These ESCRT components have been isolated and studied in a number of organisms including yeast and humans. A eukaryotic signature protein, the machinery is found in all eukaryotes and some archaea.

Retroviral matrix proteins are components of envelope-associated capsids of retroviruses. These proteins line the inner surface of viral envelopes and are associated with viral membranes.

<span class="mw-page-title-main">VPS37A</span> Protein-coding gene in the species Homo sapiens

Vacuolar protein sorting 37 homolog A is a protein in humans that is encoded by the VPS37A gene. It is a member of the endosomal sorting complex required for transport (ESCRT) system.

Paul Darren Bieniasz is a British-American virologist whose main area of research is HIV/AIDS. He is currently a professor of retrovirology at the Rockefeller University. He received the 2015 KT Jeang Retrovirology Prize and the 2010 Eli Lilly and Company Research Award. Bieniasz has been a Howard Hughes Medical Institute investigator since 2008.

In the management of HIV/AIDS, HIV capsid inhibitors are antiretroviral medicines that target the capsid shell of the virus. Most current antiretroviral drugs used to treat HIV do not directly target the viral capsid. Because of this, drugs that specifically inhibit the HIV capsid are being developed in order to reduce the replication of HIV, and treat infections that have become resistant to current antiretroviral therapies.

References

  1. "Members - U of U School of Medicine - | University of Utah". medicine.utah.edu. Retrieved 2020-04-08.
  2. 1 2 "Wesley I. Sundquist '81 | Class of 1981 | Carleton College". apps.carleton.edu. Retrieved 2020-04-08.
  3. "Research - | University of Utah". medicine.utah.edu. Archived from the original on 2020-02-11. Retrieved 2020-04-08.