Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

Abstract

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology.

Animal Models Used in Hepatitis C Virus Research

“…Work with GBV-B has proven useful to understand the pathogenesis of hepatotropic viruses and to demonstrate candidate antiviral activity. Both the infection rate, and severity of acute infection following exposure to GBV-B in tamarins [88,89] and marmosets [90] is comparable to that of HCV infection in humans. Experimental GBV-B infection induces viremia and mild acute hepatitis for an average of ten weeks in tamarins and two to three months in marmosets.…”

Distantly related hepaciviruses share common entry factor, Claudin-1

“…Tamarin sera. Archived sera from GBV-B infected red-bellied tamarins (Saguinus labiatus) were available from a previous study [17].…”

“…Infectivity over background at similar level as HCVpp could only be obtained when GBVBpp were produced using codon optimized E1E2 sequences, which was therefore chosen for the production of GBVBpp. These pseudotyped particles were then tested against archived serum from a tamarin experimentally infected with GBV-B [17] (Figure 1B). Infectivity of GBVBpp was inhibited in a dose dependant manner by serum from GVB-B infected tamarins, but not by serum from a naïve tamarin (Figure 1C); this is consistent with specific entry driven by GBV-B E1E2 and indicates that GBVBpp represents a suitable model for entry and serological studies.…”

“…In fact, GBV-B has yet to be isolated from any animals other than those experimentally infected [14,16]. Nonetheless, due to HCV's restricted host tropism, infection of small New World monkeys (tamarins, marmosets, owl monkeys) with GBV-B has previously been employed as a surrogate to study HCV disease and correlates of protections [17][18][19][20][21]. GBV-B, like HCV, is associated with hepatitis and is primarily found in the liver of the infected host [22,23].…”

GB Virus B and Hepatitis C Virus, Distantly Related Hepaciviruses, Share an Entry Factor, Claudin-1

“…In fact, GBV-B has yet to be isolated from any animals other than those infected experimentally ( 14 , 16 ). Nonetheless, due to HCV’s restricted host tropism, infection of small New World monkeys (tamarins, marmosets, and owl monkeys) with GBV-B has previously been employed as a surrogate to study HCV disease and correlates of protection ( 17 – 21 ). GBV-B, like HCV, is associated with hepatitis and is found primarily in the liver of the infected host ( 22 , 23 ).…”