Viruses: More Friends Than Foes (Revised Edition). Karin Moelling
very difficult to do. The tiger mosquitos have reached south European countries. They can resist cold temperatures and multiply in water puddles. This is a new outbreak — but will not be the last one.
HIV as an example
Early one morning, about thirty years ago, during my summer vacation in the Provence in France, I tried to contact my co-worker Jutta in Berlin. “Jutta, they are reporting accidents in a newspaper and the death of a technician working with HIV in US laboratories. Stop working with HIV, throw everything directly into the steam autoclave and kill all the virus samples immediately — this may be life-threatening.” She did not want to! “Can’t I finish the experiment first? I will be careful!” This was the typical reaction of a scientist. I remember, when we looked at a virus preparation of HIV in a centrifuge tube, it was turbid, from all the viruses that we had grown in the laboratory. We were playing with our lives without knowing it. I once gave a virus sample to the stewardess during an overseas flight to put into the refrigerator, next to food for passengers — it was in a capped tube and there was no danger.... Still! Jutta even ran an HIV test in the laboratory for a co-worker to determine his HIV status. What would have happened if he had been positive? Being HIV-positive was a death sentence in those days.
Infectious diseases are, worldwide, the most frequent cause of death. In Germany 60,000 people, and worldwide 80 million people, die of infectious diseases every year. HIV contributes 2 million cases of death per year. A similar number of people become newly infected. By comparison, 8.2 million people die of cancer worldwide each year. At the end of the 1970s infectious diseases were thought to be under control by antibiotics. This optimism vanished with the appearance of HIV/AIDS and turned into fear and pessimism. Even panic arose, as reported during times of the terrible Plague of Justinian in the Eastern Roman Empire around 541. For HIV everything was unknown: spreading, infection routes, diagnosis, and the course of the disease. It was a lucky coincidence that just at that time novel technologies for understanding diseases were becoming available: molecular biology and gene technology. The age of molecular cloning, recombination of DNA fragments of genes, the highly sensitive polymerase chain reaction (PCR) for detecting very small amounts of genetic material by amplification in the test-tube became available. All that was ready to go into research and ended up in one of the most incredible success stories of medicine, such as had never been experienced before. The only element still missing today is a vaccine. This is the conclusion after 35 years of intensive research. The virus was sequenced in almost no time; one could grow and amplify virus production in the laboratory, which enabled researchers and pharmaceutical companies to screen for drugs and to develop reliable diagnostic tests and methods for screening blood supply. In the meantime more than 30 drugs have been approved for anti-HIV therapy. Recently, a rapid diagnostic test has become available to test the HIV status of a potential sexual partner before entering a male sauna; it is fast, albeit not entirely reliable. Self-testing leads to fewer infections. Today nobody should die of AIDS in the Western world, with health insurance to cover the expenses of therapies — which still amount to about 20,000 dollars per year. The challenge is to support the poor, even in rich countries. The approach of suppressing multi-drug-resistant HIV infections by three drugs, “HAART” (highly active anti-retroviral therapy), the “triple therapy” has become a concept for other infectious diseases and also for cancer — if there are enough drugs available. HIV infection then allows the patient to lead an almost normal life, with a life expectancy similar to that of an uninfected person, i.e., about 75 years in the Western world. In the Third World the survival time is about 11 years after diagnosis, often with only a double therapy (ART, anti-retroviral therapy) and late beginning of treatment. In the Western world a normal family life can be led, with uninfected children being born. “Therapy as prevention” is the motto, indicating that no infection should occur if a patient adheres strictly to the therapeutic regimen. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) were launched in 2012 and have enjoyed great success, leading to an “almost-healing”. Depending on the drugs the “morning-after-pill” has to be taken within hours or a day. Thus, healthy people can stay healthy, while therapy of infected people is at the same time a prophylaxis for the uninfected partners. This may be the best we shall have for quite some time, until a vaccine (perhaps) becomes available one day. Complete removal of the virus from a person‘s body, a cure, is not yet possible but is a new ambitious goal. The virus changes and persists in reservoirs where it is inaccessible to therapies. However, the viral load (VL) is reduced by the triple therapy from a billion particles to about 20 per milliliter of blood. This is the limit of detection in diagnostics based on the highly sensitive PCR gene amplification method mentioned above.
Football and retroviruses are icosahedrons. Retroviruses can cause AIDS by immune suppression but once built the human placenta, so that we do not need to lay eggs.
Cell with nucleus and mitochondrium (former bacterium), DNA is the genome, RNA is the messenger for protein synthesis.
This dramatic reduction of the viral load raised the question as to whether someone treated successfully would be infectious at all. That would mean that precautions during sexual intercourse would no longer be necessary — so ran the argument. Interestingly it was Switzerland where this was discussed first, where people are more safety-oriented than in any other country. The proposal set off a worldwide debate, but was finally accepted. Consequently, one would no longer have to inform a partner about one‘s status, one’s own HIV infection. But adherence and the patient’s compliance are strict prerequisites — and severe limiting factors.
35 years of HIV research were celebrated in 2013 with a symposium at the Institut Pasteur in Paris. There the Nobel price laureate for the discovery of HIV, Françoise Barré-Sinoussi invited researchers from around the world. A noted non-participant at the meeting was Luc Montagnier, head of the department where the discovery was made, who shared the Nobel prize (2008). It was interesting to learn that Montagnier has meanwhile completely abandoned research and evidence-based therapeutics against HIV infections and turned his interest towards “alternative medicine” with natural plant extracts. This is not generally accepted.
The first electron micrograph of the virus was shown again, a historical slide. Already in the initial picture one could see that the virus changes its internal structures owing to the action of the viral protease: the virus matures after it has left the cell. This step is prevented by protease inhibitors — one can see the effect of the drug. The immature virus is no longer infectious. This electron-microscope picture was of historical importance, because Robert C. Gallo, at that time at the National Institute of Health in Bethesda, published it as his own picture. Françoise showed me the two pictures on her pinboard. Protests from the scientific community finally resulted in the declaration that there had been a mistake, pictures had been confused, the “wrong” one was published in error. Some co-workers then emigrated to other countries. The journalists, however, did not want to let go. Gallo had received the virus from Luc Montagnier, who generously gave samples of it to other researchers. Out of a mixture of viruses prepared in Gallo’s laboratory a viral candidate grew up, which however, turned out to be Montgnier’s isolate. Virologists normally do not mix virus isolates — on the contrary, they isolate individual clones — however, mixing and masking is what had happened. The French and the US governments finally reached a compromise according to which both sides would share the patent royalties. After all, Gallo had identified a very important growth factor (called Interleukin IL-2), which allowed propagation of the virus in cell culture, an important contribution to the development of a diagnostic test. Only HIV has such a fast mutation rate that no two virus isolates in the world are identical. A few point mutations, which were different in the “Gallo virus isolate”, were the basis for a defense by the lawyers, but did not prove an independent isolate. For ten years Gallo was under attack. This cost him the Nobel prize in spite of three excellent papers in the Journal Science shortly after the discovery of the virus. Furthermore, Gallo discovered the human T-cell leukemia virus HTLV-1, which is endemic in Japan and only distantly related to HIV.