Steven Foung

Clinical Focus

• Pathology
• Pathology and Laboratory Medicine

Administrative Appointments

• Associate Chair for Academic Affairs, Stanford University School of Medicine - Pathology (2004 - present)

Professional Education

Postdoctoral Advisees

Yong Wang

Research Interests

Our research has focused on the early events of hepatitis C virus infection- virus attachment and entry to susceptible cells. The approach is through the generation of human monoclonal antibodies (HMAbs) to the virus envelope proteins with an emphasis on antibodies to conformational epitopes. A large panel of HMAbs has been produced with many broadly reactive to different HCV isolates common in the US and elsewhere. Functional studies showed some inhibiting the interaction of HCV envelope E2 protein with a putative receptor, CD81. Other studies found that these antibodies identify determinants on the surface of a recombinant virus particle (HCVpp) that resembles native infectious virions. The determinants are clustered in three distinct domains that appear to be similar to the antigenic structural and functional domains of other flavivirus envelope proteins. A finding supporting this model is that two of the three domains contain determinants that mediate virus neutralization as tested by the ability to block HCVpp infection in target cells. More recent findings with infectious HCV virions from cell culture confirmed early findings with HCVpp. Our findings support the view that virus entry is mediated by only specific determinants on the virus surface and appear to be restricted to distinct immunogenic domains. This is in contrast for other viruses, such as HIV, where the convention is that neutralization is the result of a critical number of any binding sites being occupied and preventing virus entry through steric hindrance. We intend to pursue studies on expanding this model of the virus envelope, which will be important in linking structure and function.

Publications

• CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. Witteveldt J, Evans MJ, Bitzegeio J, Koutsoudakis G, Owsianka AM, Angus AG, Keck ZY, Foung SK, Pietschmann T, Rice CM, Patel AH. J Gen Virol. 2009; 90 (Pt 1): 48-58
• Antigen-specific proteolysis by hybrid antibodies containing promiscuous proteolytic light chains paired with an antigen-binding heavy chain. Sapparapu G, Planque SA, Nishiyama Y, Foung SK, Paul S. J Biol Chem. 2009; 284 (36): 24622-33
• Antibody-dependent enhancement of hepatitis C virus infection. Meyer K, Ait-Goughoulte M, Keck ZY, Foung S, Ray R. J Virol. 2008; 82 (5): 2140-9
• In vitro selection of a neutralization-resistant hepatitis C virus escape mutant. Gal-Tanamy M, Keck ZY, Yi M, McKeating JA, Patel AH, Foung SK, Lemon SM. Proc Natl Acad Sci U S A. 2008; 105 (49): 19450-5
• Hepatitis C virus (HCV)-induced immunoglobulin hypermutation reduces the affinity and neutralizing activities of antibodies against HCV envelope protein. Machida K, Kondo Y, Huang JY, Chen YC, Cheng KT, Keck Z, Foung S, Dubuisson J, Sung VM, Lai MM. J Virol. 2008; 82 (13): 6711-20