Recommended Readings: Ian A. Wilson D. Phil., D. Sci., Friday February 10, 2017

Friday Lectures

Friday, February 10, 2017   3:45 p.m.

Caspary Auditorium

Ian A. Wilson  D. Phil., D.Sci.

Hansen Professor of Structural Biology, and

Chair, Dept. of Integrative Structural and Computational Biology

The Scripps Research Institute

Broad Neutralization of Influenza Viruses and

Implications for a Universal Vaccine and Therapy

Recommended Readings:

Dreyfus, Cyrille; Laursen, Nick S.; Kwaks, Ted; et al.  (2012). Highly Conserved Protective Epitopes on Influenza B Viruses.  SCIENCE, 337(6100): 1343-1348 

Walker, Laura M.; Huber, Michael; Doores, Katie J.; et al. (2011).  Broad neutralization coverage of HIV by multiple highly potent antibodiesNATURE , 477(7365): 466-U117

Ekiert, Damian C.; Friesen, Robert H. E.; Bhabha, Gira; et al. (2011).  A Highly Conserved Neutralizing Epitope on Group 2 Influenza A VirusesSCIENCE,  333(6044): 843-850 

Gottlieb, Tanya; Ben-Yedidia, Tamar.  (2014)  Epitope-based approaches to a universal influenza vaccine.  JOURNAL OF AUTOIMMUNITY.  54 (Special Issue: SI ):15-20 

He, Fang; Prabakaran, Mookkan; Kumar, Subaschandrabose Rajesh; et al. (2011), Monovalent H5 vaccine based on epitope-chimeric HA provides broad cross-clade protection against variant H5N1 viruses in miceANTIVIRAL RESEARCH,  105: 143-151 

Li, Zhuo; Gabbard, Jon D.; Mooney, Alaina; et al. (2013). Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses.  JOURNAL OF VIROLOGY,  87(10): 5985-5993

Huber, Victor C.; Thomas, Paul G.; McCullers, Jonathan A. (2009).  A multi-valent vaccine approach that elicits broad immunity within an influenza subtypeVACCINE,  27(8): 1192-1200

Recommended Readings: Paul Bieniasz, Ph.D., December 14th

Monday Lecture Series
Monday, December 14, 2015
4:00 p.m., Carson Family Auditorium (CRC)

Paul Bieniasz, Ph.D.
Professor and Head,
Laboratory of Retrovirology,
The Rockefeller University and Aaron Diamond AIDS Research Center
Investigator, Howard Hughes Medical Institute

Retroviruses vs. Cells in Ancient and Modern Times

Recommended Reading

Empirical Articles

Busnadiego, I., Kane, M., Rihn, S. J., Preugschas, H. F., Hughes, J., Blanco-Melo, D., … & Wilson, S. J. (2014). Host and viral determinants of Mx2 antiretroviral activity. Journal of Virology, 88(14), 7738-7752. doi:10.1128/JVI.00214-14.

Hatziioannou, T., Del Prete, G. Q., Keele, B. F., Estes, J. D., McNatt, M. W., Bitzegeio, J., … & Bieniasz, P. D. (2014). HIV-1–induced AIDS in monkeys. Science, 344(6190), 1401-1405. doi:10.1126/science.1250761.

Kane, M., Yadav, S. S., Bitzegeio, J., Kutluay, S. B., Zang, T., Wilson, S. J., … & Bieniasz, P. D. (2013). MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature, 502(7472), 563-566. doi:10.1038/nature12653.

Kutluay, S. B., Zang, T., Blanco-Melo, D., Powell, C., Jannain, D., Errando, M., & Bieniasz, P. D. (2014). Global changes in the RNA binding specificity of HIV-1 gag regulate virion genesis. Cell, 159(5), 1096-1109. doi:10.1016/j.cell.2014.09.057.

Rihn, S. J., Hughes, J., Wilson, S. J., & Bieniasz, P. D. (2015). Uneven genetic robustness of HIV-1 integrase. Journal of Virology, 89(1), 552-567. doi: 10.1128/JVI.02451-14.

Review Papers

Malim, M. H., & Bieniasz, P. D. (2012). HIV restriction factors and mechanisms of evasion. Cold Spring Harbor Perspectives in Medicine, 2(5), a006940.  doi:10.1101/cshperspect.a006940.

Scientists Spot New Clues to HIV-Linked Dementia

Researchers have identified two genetically distinct types of HIV in the cerebrospinal fluid (CSF) of patients with HIV-associated dementia.   The discovery may help explain why the risk of developing neurological difficulties increases as AIDS patients live longer, and may also help predict which patients are at greatest risk for the problem, according to the U.S. scientists.  They said the two newly-identified HIV types aren’t being detected in HIV that circulates in a patient’s blood, and one type may be present cerebrospinal fluid years before the onset of HIV-linked dementia.  The fact that the two HIV types can be detected in the CSF indicates that they grow in the central nervous system. 

The study, which appears in the journal PLoS Pathogens, was led by researchers at the University of North Carolina at Chapel Hill School of Medicine.

Gamers Solve Protein Puzzle That Stumped Science

What has taken researchers more than a decade to chip away it, gamers solved in weeks.   Foldit players have solved the structure of a retroviral protease of the Mason-Pfizer monkey virus; their solution and its validation appear in a paper published online in advance in Nature Structural & Molecular Biology this week. The University of Washington’s David Baker, the Foldit creator, tells Nature‘s News blog that “the M-PMV structure had stumped scientists for a very long time before Foldit players made their breakthrough, adding: “This is the first example I know of game players solving a long-standing scientific problem.”

Research Sheds Light on Cause of Brain Deficits in HIV Patients

Some HIV patients experience memory loss and other neurological deficits, despite treatment, and new research suggests that the reason why is because the virus weakens the blood-brain barrier by infecting a small group of supporting brain cells called astrocytes.   The finding, published in the June 29 issue of the Journal of Neuroscience, may help explain why 40 percent to 60 percent of HIV patients on antiretroviral therapy experience mild to moderate neurological problems such as learning difficulties.

Scientists reveal HIV weakness

Development of an HIV vaccine has been seriously hampered by the fact that the retrovirus mutates so rapidly.  In a new finding that may allow vaccine designers to sidestep part of that obstacle, researchers at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University have identified sections of an HIV protein where mutations would actually undermine the virus’ fitness — its ability to survive and reproduce. Vaccines that prime immune cells to specifically target those vulnerable regions could prove much more effective than previously tested vaccines.   Read these latest HIV research findings in PNAS Early Online.

Recommended Readings: Sarah Schlesinger M.D. March 7, 2011

Monday Lecture Series

Vaccines that Target Dendritic Cells

Sarah Schlesinger  M.D.

Senior Attending Physician and Associate Professor of Clinical Investigation

 Cellular Physiology and Immunology

March 7, 2011

4:00 p.m.-5:00 p.m. Caspary Auditorium

Recommended Readings

Dhodapkar MV; Sznol M; Wang D, et al.  2010.  Early development of CDX-1401, a novel vaccine targeting NY-ESO-1 to the dendritic cel receptor DEC-205.  Journal of Immunotherapy.  33(8):895-896   Request Article from Markus Library. 

Wanialla CN; Faul EJ; Gomme EA, et al.  2010.  Dendritic cells infected by recombinant rabies virus vaccine vector expressing HIV-1 Gag are immunogenic even in the presence of vector-specific  immunityVaccine.  29(1):130-140

Fiorentini S; Giagulli C; Caccuri F, et al.  2010.  HIV-1 matrix protein p17: a candidate antigen for therapeutic vaccines against AIDS.   Pharmacology & Therapeutics.  128(3):433-444  Request Article from Markus Library.

De Groot A; Buhlmann J; Weber C, et al.  2010.  De-Tolerization of anti-DEC-205 for HIV vaccine delivery.  (abstract only)  AIDS Research and Human Retroviruses.   26(10):A135-A136

Ahlers, JD; and  IM Belyakov.  2009.  Strategies for optimizing targeting and delivery of mucosal HIV vaccinesEuropean Journal of Immunology.  39(10):2657-2669

Kloverpris HN; Karlsson I; Thorn M, et al.  2009.   Immune hierarchy among HIV-1 CD8+T cell epitopes delivered by dendritic cells depends on MHC-I binding irrespective of mode of loading and immunization of HLA-A*0201 mice.  APMIS  117(11):8489-855

Demberg T; and M. Robert-Guroff.  2009.  Mucosal immunity and protection against HIV-SIV infection: strategies and challenges for vaccine design.  International Reviews of Immunology.  28(1-2):20-28   Please request from Markus Library.

Gruber A; Chalmers AS; Rasmussem RA, et al.  2007.  Dendritic cell-based vaccine strategy against human immunodeficiency virus clade C: skewing the immune response toward a helper T cell type 2 profile.   Viral Immunology.  20(1):160-169.

The Use of siRNA Techniques To Silence HIV

Prof. Jyoti Chattopadhyaya from Uppsala University and colleagues from India have synthesised modified siRNAs targetting the TAR region of HIV-1, some of which exhibit a four-fold enhanced half-life in serum over the native unmodified siRNA. The best compound synthesised had an IC50 more than three-fold lower than that of the native and two-fold lower than that of the existing locked nucleic acid (LNA) modified counterpart.  The strategy to chemically modify the native siRNAs by substitution with the jcLNA can be considered as a significant development, leading to both enhanced siRNA efficiency and serum stability over that of the native.  Read more in MedChemComm.

Cellular Protein Hobbles HIV-1

A cellular protein called BST-2 had already been known to interfere with the spread of human immunodeficiency virus type 1 (HIV-1), by inhibiting the release of its progeny particles from infected cells. Now a team from McGill University, Montreal, shows that in addition, each progeny virion’s ability to cause infection is severely impaired.

“BST-2 may exert a more potent inhibition effect on HIV-1 transmission than previously thought,” says coauthor Chen Liang. The research is published in the December Journal of Virology.