The basic facts about the virus

Doctors knew the symptoms of hepatitis long before they knew exactly what caused them. By the 1930s scientists knew that there were two kinds of hepatitis­infectious hepatitis, transmitted largely by food or water, and serum hepatitis, transmitted by contact with blood. While they could distinguish these two diseases clinically, no one knew what organism was involved. Although the beliefs about the means of transmission of the two diseases would later have to be revised somewhat (as you know if you have read the previous two chapters of this book), it was eventually discovered that there were two different viruses causing these illnesses, later designated hepatitis A (infectious hepatitis) and hepatitis B (serum hepatitis). The virus that causes hepatitis B was isolated in the 1960s, and by 1973 the virus that causes hepatitis A was also discovered.

A New Kind of Hepatitis

Then, starting in the 1970s, doctors began to notice a disease they hadn’t seen before. It looked like hepatitis with symptoms very much like those of hepatitis A and hepatitis B, and the same kind of liver involvement while it seemed to have a more chronic course than either HAV or HBV, it was still clearly some kind of hepatitis. But when patients with this disease had their blood tested, neither hepatitis A nor hepatitis B showed up. So physicians began calling the new disease “non-A, non-B hepatitis.” It was noticed fairly early on that this disease was transmitted in blood transfusions. In fact, about 10 percent of people who got frequent transfusions­hemophiliacs, for example-would come down with some kind of liver inflammation, often the non-A, non-B disease, but there was nothing anyone could find in the blood supply that would account for the problem. The increases were also noticed in Japan, where rising rates of cirrhosis made people suspect that some pathogen might be the cause.

There were other hints. Studies showed that injection drug users, health care workers, people who lived with hepatitis sufferers, and people with many sexual partners were all at higher risk for developing this new kind of hepatitis. There was no question that there was something being carried in blood that was moving from one person to another.

In the late 1980s scientists began closing in on the virus. Using serum from a person infected with non-A, non-B hepatitis, they were able to cause the mysterious disease in a chimpanzee (chimps and tamarin monkeys are the only other species known to be susceptible to the disease). So they knew they had infected blood. Next they extracted blood from the animal and isolated the plasma. Then they centrifuged the infectious plasma, spinning out a tiny pellet that contained the viral particles and nucleic acids.

The next step was to “denature” the proteins-break them into their component parts. Organisms called phages can pick up these small bits of nucleic acid and express them on their surfaces. This creates a “library” of all the different genetic materials found in the original sample. These phages were then cloned to make many copies of the “books” in the phage library.

Then the researchers took blood from two chimps, one that had been exposed to non-A, non-B hepatitis and one that had not been, and tagged all the antibodies from the two samples with chemical markers so that they could be identified.

Finally, they put the tagged antibodies from the uninfeeted sample into plates holding one copy of the entire phage library, and antibodies from the infected sample into another copy of the library. They then compared the two, and found that antibodies from the infected sample attached to one more phage clone than the antibodies from the uninfected sample. This showed that there was an expression of viral proteins from the infected sample that did not appear in the uninfected sample. Later they found that the protein was an RNA virus. By identifying the unique antibody, the researchers could develop a screening test for the HCV infection.

For the first time, a molecular biological technique­the cloning of nucleic acid-had been used to identify a disease agent that had never been seen, cultured, or defined by the antibodies that attack it. Because these researchers worked for a profit-making company, one of the first things they did when they found the virus was to patent it.

The stock of the company, Chiron, shot up immediately because people hoped that a profitable vaccine would soon follow. But now, more than ten years later little more than diagnostic blood tests for the virus have been produced, and, like many stocks that soar on promises of unrealized “scientific breakthroughs,” Chiron’s has settled back to former levels. But research goes on at Chiron and in other places. One of the large probles faced by those trying to develop a drug treatment for HCV is that the virus thrives and reproduces inside the cell rather than on its surface, and it is very difficult to design a drug that will penetrate the cell wall. But it’s not impossible-the protease inhibitors that have revolutionized the treatment of HIV are an example of a “small molecule” drug that does this.

Tagged under:Diseases doctors hepatitis hepatitis a hepatitis c nucleic acids plasma serum hepatitis virus

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