Combined ID / IIDR Rounds – Wednesday, March 7th, 2018
Author: Christy Groves
Hepatitis B is a deadly viral infection that attacks the liver and causes acute and chronic disease. Currently, the Hepatitis B virus (HBV) infects approximately 3.5% of the global population and up to 6% in critical areas of Southeast Asia and Sub-Saharan Africa. At this month’s ID / IIDR Combined Rounds, infectious disease physician Dr. Zain Chagla and evolutionary geneticist Dr. Hendrik Poinar present their clinical and research-based work to discuss the origin, current status, and future outlook of HBV.
Dr. Chagla began the presentation by introducing HBV as a “neglected tropical disease”. During the 1990s, a successful HBV vaccination became widely popularized, subsequently leading to little emphasis being placed on the need for effective HBV medications. Today, although this vaccination has been successful in decreasing the global incidence of HBV, the lack of effective treatments against those already infected has allowed HBV to greatly devastate many areas of the world. Moving forward, controlling HBV on a global scale requires the development and integration of effective screening and treatment strategies.
Given its unique virology and life cycle, amongst other characteristics, Dr. Chagla went further to explain why designing therapeutics for HBV remains especially difficult in comparison to other major viral diseases. However, several promising treatment options have recently entered the clinical pipeline, including various viral entry inhibitors, secretion inhibitors, and nucleoside analogues. Chagla explained how these treatments, although in their earlier stages of development, offer hope for a more positive future.
Evolutionary geneticist Dr. Hendrik Poinar followed Dr. Chagla with a discussion of HBV from a historical standpoint. Poinar’s talk largely centered around how the application of various DNA sequencing methods helps answer evolutionary-related questions regarding the emergence of pathogenic strains.
Dr. Poinar first explained how, after death, the body undergoes decomposition and exudes organic material into its surrounding environment. With time, these molecules undergo a number of changes that cause the DNA to degrade. Because any given sample can include as little as .001 percent of the target material, Poinar discussed how one could apply a technique called targeted enrichment to the sample to increase the ratio of DNA for sequencing. Poinar presented how his team applied this technique to identify and reconstruct the smallpox virus from mummies within a crypt in Lithuania. Further, he explained how – unlike HBV – smallpox expresses much more timely data regarding its origin and evolution.
Poinar then presented his most recent study, in which his team analyzed the DNA of the mummified remains of a medieval child buried in the Basilica of Saint Domenico Maggiore in Naples, Italy. Previously thought from paleopathological analyses (without DNA testing) to have expressed the first case of smallpox, Poinar’s team found no evidence of the variola virus within the mummy’s DNA. Instead, through the application of targeted enrichment, the team was surprised to find a genetic match with a similar HBV as is seen in modern-day samples. After ruling out the possibility of contamination and finding evolutionary comparisons amongst other mummies exemplifying modern viral populations, Poinar’s team was able to sequence the complete genome of an ancient strain of HBV and provide evidence suggesting that HBV has existed amongst populations for centuries.
In conclusion, Dr. Chagla’s and Dr. Poinar’s presentation of HBV emphasizes the importance of gaining a multidisciplinary understanding of infectious diseases – a better knowledge of the biology, socioeconomics, and evolutionary history of a pathogen can lead to more innovative ways to trace and control them.
- Read “The paradox of HBV evolution as revealed from a 16th-century mummy” in PLoS Pathogens.