Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity

Abstract

Hepatitis B virus has infected a third of the world’s population, and 296 million people are living with chronic infection. Chronic infection leads to progressive liver disease, including hepatocellular carcinoma and liver failure, and there remains no reliable curative therapy. These gaps in our understanding are due, in large part, to a paucity of animal models of HBV infection. Here, we show that rhesus macaques regularly clear acute HBV infection, similar to adult humans, but can develop long-term infection if immunosuppressed. Similar to patients, we longitudinally detected HBV DNA, HBV surface antigen, and HBV e antigen in the serum of experimentally infected animals. In addition, we discovered hallmarks of HBV infection in the liver, including RNA transcription, HBV core and HBV surface antigen translation, and covalently closed circular DNA biogenesis. This pre-clinical animal model will serve to accelerate emerging HBV curative therapies into the clinic.

An enrichment protocol and analysis pipeline for long read sequencing of the hepatitis B virus transcriptome

“…Although individual splicing events are readily detectable, the assignment of multiple splicing events is unreliable [10]. Long read sequencing approaches have been available for several years [21,22,44], however it is only recently that their accuracy has improved to a level (>99 %) where they offer an alternative to short read methods. The PacBio sequencing platform is becoming more widely available and, combined with approaches that allow for multiplexing of samples, is financially competitive with more established platforms.…”

Pathogen Detection Using Metagenomic Next-Generation Sequencing of Plasma Samples from Patients with Sepsis in Uganda

“…In total, 263 samples (254 plasma samples, 4 healthy human plasma samples, and 5 water controls) were indexed and pooled using the Nextera DNA Flex library prep kit and run on an Illumina Hiseq 2500 system to obtain 150-bp paired-end reads. Confirmatory qPCRs were performed on the extracted plasma for HIV, EBV, and hepatitis B virus using previously described primers and probes ( 13 , 38 – 40 ).…”

Forthcoming Developments in Models to Study the Hepatitis B Virus Replication Cycle, Pathogenesis, and Pharmacological Advancements

“…Another new model is macaque primary hepatocytes . With the help of these new models, curative treatment is possible.…”

“…5 Another new model is macaque primary hepatocytes. 145 With the help of these new models, curative treatment is possible. The attempts are hampered, with the dearth of a physiologically appropriate, animal model of chronic HBV disease.…”