The virus which killed millions and the Nobel prize 2020

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The virus which killed millions and the Nobel prize 2020

Saturday, 17 October 2020 | Dr Rajendra kumar Jha

Nobel prizes often bring surprises but not this year, in 2020, when it was awarded to Harvey Alter, Michael Houghton and Charles Rice for the discovery of Hepatitis C virus which is by far the most important virus causing inflammation of Liver leading to liver cirrhosis and cancer which is a larger menace than HIV , and equals Tuberculosis annually in numbers.

This Prize was long overdue in recognition of great saga of scientific journey of almost fifty years. This discovery was responsible for saving millions of lives from the disease called Viral Hepatitis C and in the process structured a new path for future growth and unique application of a novel strategy in molecular biology, which has helped in the making of a vaccine now against COVID19 too.

There are two sets of viruses  which produce Hepatitis, the  first group is much more prevalent in India and developing countries. They are often fast paced with obvious symptoms of jaundice but benign  in its course. They are known as Hepatitis A and E which enter human system through contaminated food or water. These enteric viruses are RNA viruses with a short incubation period and acute onset of jaundice which heal without much problem on its own. Hepatitis E virus is a benign virus much like A except when it infects pregnant females.

The other set of viruses which are often known as Serum or transfusion associated Hepatitis  virus enter  human  system through blood or body fluids. They are Hepatitis B, Hepatitis D (DNA viruses) and Hepatitis C (RNA Virus). Hepatitis D virus is very similar to Hepatitis B where as Hepatitis C is totally different from B virus. These Serum Hepatitis viruses are far more complicating and  lethal if not diagnosed early. They generally present with longer incubation period than Hepatitis A or E, often remain elusive with fewer and milder symptoms such as generalised weakness, loss of appetite and occasionally yellow discolouration of conjunctiva. It may remain totally asymptomatic in its protracted course yet at the end may lead to total destruction of liver and even cancer almost unnoticed.

Until 1960's transfusion of blood was done without adequate care which caused many mysterious deaths due to liver failure. Such was the infectivity  that as many as one in three (>30% ) used to get infected with serum hepatitis viruses following surgical procedures, multiple blood transfusions or through per cutaneous infected needles. The discovery of Hepatitis B virus in 1967 by Baruch Blumberg and subsequent development of immunoassay for Australia antigen (first isolated from a Hepatitis B patient of Australian aboriginal descent) got him the Nobel prize for medicine in 1976, paving the way to routine screening and detection of Hepatitis B virus  before blood transfusion and in surgical practice.

The Author is Currently Professor of medicine at Manipal Tata Medical College and Formerly Professor and Head, RIMS.

It also led to development of successful vaccine to prevent Hepatitis B in due course. However, Hepatitis B constituted only 20% of total Serum Hepatitis cases and the rest 80% were non A non B type,the cause of which were unknown then .

Therefore, non B Hepatitis serum had to be first screened for some form of orally entering Hepatitis A Virus (HAV), erroneously presumed to have  entered into serum.

Hepatitis A virus was discovered in 1975 by a team of scientists led by Feinstone and Purcell. Once a negative test was obtained for Hepatitis A ,it firmly  put the focus on unknown virus as the cause.

Then came HARVEY J ALTER, a transfusion physician at NIH(USA) who for the first time declared that this putative causative agent had shorter incubation period than Hepatitis B virus and had very mild  or almost asymptomatic  clinical course. He could also find a primate model (chimpanzees)  after a long search paving the way for much needed acceleration in research.

Dr  Alter with the help of Dr Purcell also ascertained certain physical characteristics of this putative virus such as its lipid envelope and its likely size measuring 30 to 60 nm.  Surprisingly, nothing much moved for next ten years.

In 1982 MICHAEL HOUGHTON of Chiron Corporation got into the hunt of this virus with a novel molecular approach by screening DNA fragments ( cDNA) isolated from infected chimpanzees blood.

With the introduction of lambda bacteriophage system his team  could find a new colony of bacteriophage(a virus infecting bacteria) which was different from both host and viral Hepatitis B. This cloned DNA fragment led to reconstruction of a new virus whose Genetic structure could be established now.

However, it was yet to be  conclusively proved that this newly found viral particle  containing the complementary RNA virus was the aetiological agent.

CHARLES RICE. while working at the Washington university developed a viral RNA of the putative virus containing conserved non coding 3’ region, responsible for viral replication. When injected into the primate model, the chimpanzees, it started its replication producing a condition identical to Human viral C hepatitis.

The work of Charles Rice finally established the cause - effect relationship and the virus was  recognised and was named as Hepatitis C virus.

With the introduction of sub genomic clones of HCV by Ralph bartenschlager, the research on antiviral therapy got accelerated and series of drugs and therapeutic agents were discovered leading to very effective therapy which has the potential to save from near certain death .However, an effective vaccine against Hepatitis C virus is in pipe line and we may have soon .

The Author is Currently Professor of medicine at Manipal Tata Medical College and Formerly Professor and Head, RIMS.

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