Jay Levy, MD

Research Associate, Cancer Research Institute
Professor
Department of Medicine: Hematology/Oncology
+1 415 476-4071

Research interests of our laboratory are directed at understanding the mechanisms underlying HIV pathogenesis with the hope of designing novel antiviral therapies and an effective AIDS vaccine.

Virus Studies: Biologic, serologic, and molecular characterization of several HIV-1 and HIV-2 strains are revealing their extensive heterogeneity and have demonstrated that viruses may evolve differently in the same individual in the immune system, bowel, and the brain. Molecular studies with intraviral recombinants of HIV-1 have shown that very few envelope gene changes can affect tissue tropism, cytopathicity and serum antibody sensitivity. Current anti-HIV experiments are evaluating siRNA approaches.

Immune Studies: Recent emphasis in the laboratory has been on anti-HIV innate immune responses. We are evaluating the role of plasmacytoid dendritic cells (PDC), major producers of type 1 interferons. Studies are directed at understanding how HIV-infected cells induce interferon production from PDC and what cell surface molecules, including toll-like receptors, are involved in this process. Another innate response we have defined is the ability of CD8+ lymphocytes to suppress HIV replication without killing the cells. This CD8+ cell noncytotoxic antiviral response (CNAR) is mediated by a novel as yet unidentified CD8+ cell antiviral factor (CAF). CNAR and CAF block HIV transcription. Certain cytokines such as IL-2, IL-15 and IFN-a as well as co-stimulation with CD3 and CD28 antibodies and co-culture with mature dendritic cells can enhance this antiviral response. 

The identity of CAF is being determined by protein purification procedures involving mass spectrometry, and molecular analyses, using microarray techniques. Other studies focus on why the CD8+ cell anti-HIV response decreases with time in HIV-infected individuals. In acute HIV infection, we have found that antiviral drugs that reduce HIV plasma loads, decrease the CD8+ cell antiviral response. New treatment directions being evaluated are IL-2 therapy, immunization, and structured treatment interruptions in attempts to restore the host anti-HIV immune response.

Vaccine Studies: Experiments towards deriving an AIDS vaccine involve an HIV-2 DNA vaccine with genetic adjuvants (GM-CSF, B7.2). Immunized baboons are monitored for anti-HIV-2 neutralizing antibodies as well as cell-mediated anti-HIV immune responses. These studies will hopefully pave the way for the development of an effective HIV vaccine for humans.

Stem Cell Studies:  With Dr. Y. W. Kan's laboratory, we are deleting the CCR5 gene (major receptor for HIV) from CD34+ hematopoietic stem cells using iPS cells generated by the TALENS and CRISPR-Cas approaches.  The resulting stem cells are resistant to HIV infection.  This research is conducted toward the development of a "cure" for HIV infection.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Virology & Microbial Pathogenesis
Research Summary: 
HIV Pathogenesis

Websites

Publications: 

Note from the Editors.

AIDS (London, England)

Levy JA, Coutinho R, Lewin S, Phair J, Mears-Brown A

Schwab M (ed.) Encyclopedia of Cancer

Human T-Lymphotropic Virus

Levy JA, Murphy EL

Discovery of another anti-HIV protein in the search for the CD8+ cell anti-HIV Factor.

Proceedings of the National Academy of Sciences of the United States of America

Levy JA