The laboratory of Robert Lanford is involved in three research
programs involving hepatitis B virus (HBV), hepatitis C virus (HCV) and
GBV-B, a surrogate model for HCV. One of the primary focuses of Lanford’s research program is to better
understand the interactions of the hepatitis virus with the host, and
how it influences either viral clearance or persistence and disease
progression. The chimpanzee is the only animal other than man
susceptible to infection with HCV, thus Lanford has studied this animal
model extensively. Using DNA microarray technology, his team currently
examines liver tissue from HCV-infected chimpanzees for changes in
expression due to viral replication of 47,000 genes and the immune
response to viral infection. Within days of infection, hundreds of
interferon response genes are increased in expression in the liver.
Although the virus manages to persist in the liver, the host limits the
spread of the virus such that only a minor fraction of hepatocytes are
infected. The data suggest that the mechanism of viral clearance during a
successful immune response is dependent on both the innate and adaptive
T cell response. In a multi-institute collaboration, Lanford recently
compared the immune response to HCV and hepatitis A virus (HAV), a virus
with many similarities to HCV, but differs in that it never induces
chronic infection. Remarkably, they discovered that during HAV
infections little to no induction of interferon response genes occurs in
the liver (Fig). Thus, the virus that evades the innate immune response
is always cleared and the one that induces a robust innate immune
response often causes chronic infection. These studies highlight the
limitations of our understanding of how HCV persist in the liver, and
the need for research on persistent viral infections to aid in vaccine
Zubkova I, Duan H, Wells F, Mostowski H, Chang E, Pirollo K, Krawczynski K, Lanford R, Major M. Hepatitis C virus clearance correlates with HLA-DR expression on proliferating CD8+ T cells in immune-primed chimpanzees. Hepatology. 2014 Mar;59(3):803-13.
Feng Z, Hensley L, McKnight KL, Hu F, Madden V, Ping L, Jeong SH, Walker C, Lanford RE, Lemon SM. A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature. 2013 Apr 18;496(7445):367-71.
Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM,
Fosdick A, Frey CR, Zheng J, Wolfgang G, Halcomb RL, Tumas DB. GS-9620,
an oral agonist of Toll-like receptor-7, induces prolonged suppression
of hepatitis B virus in chronically infected chimpanzees. Gastroenterology. 2013 Jun;144(7):1508-17, 1517.e1-10.
Yu G, Yagi S, Carrion R Jr, Chen EC, Liu M, Brasky KM, Lanford RE, Kelly
KR, Bales KL, Schnurr DP, Canfield DR, Patterson JL, Chiu CY. Experimental cross-species infection of common marmosets by titi monkey adenovirus. PLoS One. 2013 Jul 24;8(7):e68558.
Spaniel C, Honda M, Selitsky SR, Yamane D, Shimakami T, Kaneko S, Lanford RE, Lemon SM. microRNA-122 abundance in hepatocellular carcinoma and non-tumor liver tissue from Japanese patients with persistent HCV versus HBV infection. PLoS One. 2013 Oct 9;8(10):e76867.