Andrea S. Meyer

Unraveling the mystery

The Centers for Disease Control (CDC) in Atlanta, Georgia, were formally asked to assist with the investigation of a new mysterious disease that had broken out in the Four Corners, America in 1993. Specimens from the outbreak reached Atlanta on May 31; the specimen included samples from the environment, from domestic animals, from rodents found near the dwellings, and from the victims themselves. The specimens were handled at the level four, which is used for handling the most deadly agents under extreme conditions. Extracts of tissue samples were sent to the various laboratories for testing. Direct tests were used to find the genetic material of possible agents. To detect bacteria, they were spread out on a wide range of different nutrient gels. For viruses, they were inoculated into laboratory rodents, the best way to detect an unknown virus. At the same time, blood from patients was being tested for antibodies using a range of stored material from possible infectious agents. Four days after the first specimens arrived in Atlanta, the killer was identified: a hantavirus, that was found in the tissues of the lung of the victims, causing the disease that was killing them.

Three billion years

To understand where viruses come from and how something so simple can produce such large effects requires an understanding of the basic machinery that is shared by all forms of life. The instructions are contained in the code of life, the genetic code, which is written in just four letters: A, C, G, and T. These are the shorthand used to describe the subunits of deoxyribonucleic acid (DNA)—the nucleotides. Life as we know it is hugely complicated at the chemical level. In life as it is today, RNA is the servant of the genes, a messenger molecule carrying instructions from the DNA out into the machinery of the cell. However, evidence shows that RNA is actually a molecular fossil of the earliest forms of life. While DNA needs proteins to unwind it, copy it, cut it and repair its almost endless chains, the smaller RNAs can do much of this for themselves. Some viruses have genetic material like that of the cell—made of DNA—and need to use much of the cellular machinery. Others, more complicated, with more DNA genes, make most of their own machinery and only need to use the basic structure of the cell. Most viruses exist in the RNA world, however, themselves living reminders of the mechanisms of that distant past. They do not, ever, make DNA. Viruses that cause large epidemics tend to spread efficiently, and one of the most efficient routes of all is by air: aerosol spread. Some viruses infect the lungs or the tubes leading to the lungs and convert the cells lining the passages into virus factories.

How to stop a virus

This chapter focuses on the basic ways that can be used to stop a hantavirus from killing people, such as prevention, vaccination, antiviral drugs, and medical care. The chapter also discusses the ways to track down the source of the infection. The same genetic methods that allowed the rapid identification of Sin Nombre can be used to look at the genes of a virus that has caused HPS. Rodents are trapped at possible sites where the infection could have occurred and their genes are examined. Even viruses that are of the same type will have some variation, usually well below that needed to call them a new virus. Viruses from different locations will have more variation.

On the origin of viruses

This chapter explores the origin of viruses and their pathogenesis to host cells. The viruses do not need to kill their host to grow. It is in the interest of a virus not to kill or immobilize the host too quickly, as this reduces the chances for spread of the virus. Over time, both virus and host adapt so that the virus produces less severe disease in its normal host, however, this cannot hold up for every case in complex biological systems. Sometimes a virus does not need to jump species to be a new and deadly killer. A virus jumping to a new host can cause unusually severe disease; it is one of the main ways that new infections appear. When infections jump from an animal to a human they are called “zoonoses,” and many of the most severe human diseases fall into this category. Hantavirus pulmonary syndrome provides one of the best examples of this. The chapter also discusses the potential applications of viruses in biowars, genetic engineering, and biotechnology.

Hantaviruses: Out of Asia

The ecological research was being conducted in the Four Corners in the hope of learning how to prevent human cases of the disease called Hantaan infection, however, attention among the medical researchers was focused on what was known about other hantaviruses. Although this disease was new to western medicine, it had been observed before. It was also observed in Korea in 1951, during the trench war. There is a description of a disease with similar symptoms in a Chinese medical book, “Whang-Jae-Nae-Kyung,” dating from 960 A.D., almost a thousand years earlier. From among the many names the disease had gathered throughout history, it was the Russian name that was to stick: hemorrhagic fever with renal syndrome. Hantaviruses are only spread directly by body fluids and excretions of the infected rodent. It grows and infectious virus is released, at least for several months, and possibly for the whole life of the rodent host, without causing any apparent disease or any other than minor effects, such as a raised number of white cells in the blood of the mouse. However, in humans the story can be very different and deadly.

The heart of America/ the middle of nowhere

The Native Americans to whom much of this land belongs are reverent to what outsiders consider to be the mysteries of life. Completely embedded in the interior of the most highly developed country on earth, the Navajo homeland is a sovereign nation with a strong identity of its own. Modern society of America thinks of diseases as somehow “dirty” rather than as part of any ecosystem, and the southwestern desert does not present itself as unclean. Americans like to believe that disease culls the weak, the old, and the sick. The idea that Americans do not die of diseases is false. In 1993, when residents of the Four Corners began to die of an unfamiliar disease, all these outlines became important, for many different reasons. The most striking aspect of the story was that the first identified victim had been young and healthy. Four young, active individuals living in close proximity were identified as suffering from the new disease. An obvious conclusion was that they had been infected from the first identified victim during that time, which led to the major fear of another epidemic or even the worldwide version, a pandemic.

8 – Other hantaviruses

Publisher Summary This chapter discusses other types of hantaviruses such as Puumala and Dobrava, which are quite different from the hantaviruses that caused an outbreak of a flu in Four Corners in America. The disease caused by puumala is nephropathia epidemica (NE) and is far milder than the hemorrhagic kidney disease (HFRS) caused by Hantaan, but is still a very unpleasant disease, with fever, back pain, headache, and decreased urine production followed by a massive increase. The severe nature of Dobrava HFRS makes it unlikely that it has remained unnoticed in large numbers. The chapter also talks about several types of hantaviruses that have not been linked to any disease to mankind and are harmless. Hantaviruses can be divided into groups: at the genetic level there are at least seven. Hantaviruses are able to infect a wide range of host animals. At least 71 possible hosts were identified in one Chinese study, a number that includes Homo sapiens sapiens: humans.

Changes, concealment, and trojan horses

Evolution is driven by the slow tick of mutation. It proceeds faster for RNA than DNA and faster for viruses than for cells, as viruses produce such huge numbers of each new generation that changes are more likely. All viruses must at some time have arisen by mutation, but it is usually a slow process. Most mutations are the change of one letter of the genetic code, known as point mutations. Sometimes bigger changes happen, with the loss or addition of a region of the nucleic acid. Many changes have no apparent effect. Influenza is a disease not just of humans but of many other species. There are three basic types of influenza, named A, B, and C. Each virus is a twisted core of protein containing the RNA coding for the virus genes, surrounded by a fatty sheath studded with viral proteins. It is also mutation that drives the appearance of drug-resistant viruses. Although picking up new genes is more rapid for viruses with segmented genomes, there are plenty of examples in other viruses. Viruses infecting humans from an animal source can cause severe disease, and sometimes the virus does not have to make the jump. While we now know of many hundreds of viruses infecting humans, it is clear that many more remain to be discovered. Many of these will cause only mild disease, since those that cause obvious symptoms tend to be the first to be noticed.