Professor of Pharmaceutics and Adjunct Professor of Microbiology
Office Location: Health Sciences H-272K
Campus Box: 357610
Dr. Hu holds a B.A. degree with Great Distinction in Biochemistry from the University of California, Berkeley, and a Ph.D. in Molecular Biology from the University of Wisconsin. He completed his postdoctoral training in tumor virology in Dr. J.F. Sambrook's laboratory at Cold Spring Harbor Laboratory.
The primary interests of his laboratory are HIV pathogenesis and approaches for the prevention and treatment of AIDS. Currently, the staff pursues three major research areas: design and evaluation of vaccines against HIV and related primate lentiviruses; structural, functional, and immunogenic studies of HIV-1 envelope proteins; and pathogenesis of HIV-2.
Using SIV as a model, they have shown that immunization with live recombinant poxvirus and subunit vaccines protects macaques against infection by a pathogenic primate lentivirus. This model provides them with a basis to study the correlates and mechanisms of protection, to define the limits of the protective responses, and to design new approaches to augment such responses. They are also investigating to what extent such approaches could be applied towards the development of a safe and effective vaccine against HIV infection and AIDS in humans.
One of the key targets for the development of AIDS vaccines is the highly glycosylated surface antigen of HIV. Evidence suggests that these carbohydrates may contribute to the ability of the virus to escape host immune responses. The laboratory has introduced mutations in HIV-1 Env protein and shown that specific N-linked glycosylation mutants render the virus more susceptible to broadly neutralizing antibodies. They are currently examining whether these mutant Env proteins will function as better candidates of AIDS vaccines than the fully glycosylated forms.
Finally, they have developed a highly pathogenic isolate of HIV-2, which upon inoculation in pig-tailed macaques induces rapid CD4 depletion and AIDS-like diseases. They have used this model to show that post-exposure treatment with antiviral drugs, even of limited duration, is highly effective in reducing viral load and maintaining normal CD4 cell levels. They have also generated infectious and pathogenic molecular clones of this virus, which will be used to define genetic determinants that contribute to the pathogenic phenotype of this virus.
Polacino, P., Stallard, V., Klaniecki, J. E., Pennathur, S., Montefiori, D. C., Langlois, A. J., Richardson, B. A., Morton, W. R., Benveniste, R. E., and Hu, S.-L. Role of immune responses against the envelope and the core antigens of SIVmne in the protection against homologous cloned and uncloned virus challenge in macaques. J Virol 73:8201-8215, 1999.
McClure J., Schmidt A. M., Rey-Cuille M. A., Bannink J., Misher L., Tsai C.-C., Anderson D. M., Morton W. R., and Hu S.-L. Derivation and characterization of a highly pathogenic isolate of human immunodeficiency virus type 2 that causes rapid CD4+ cell depletion in Macaca nemestrina. J Med Primat 29:114-126, 2000.
Li Y., Rey-Cuille M-A., and Hu S.-L. N-Linked glycosylation in the V3 region of HIV-1 surface antigen modulates coreceptor usage in viral infection. AIDS Res Hum Retroviruses 17:1473-1479, 2001.
Rey-Cuille M.-A. and Hu S.-L. CXCR4 usage and enhanced replicative capacity of HIV-2/287, an isolate highly pathogenic in Macaca nemestrina. AIDS 15:2349-2357, 2001.
Binley JM, Sanders RW, Master A, Cayanan CS, Wiley CL, Schiffner L, Travis B, Kuhmann S, Burton DR, Hu S-L, Olson WC, Moore JP. Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins. J Virol 76:2606-2616, 2002.