Viruses: More Friends Than Foes (Revised Edition). Karin Moelling
refused point-blank to take part in animal studies, and the only technician willing to help had no license. Out of 50 co-workers nobody could help. So I cancelled all appointments in the institute and did it myself — to my own surprise I had not forgotten, during the many years at the desk, how to handle and inject mice.
Meanwhile, we tried to fulfil the request made by the Bill and Melinda Gates Foundation that HIV microbicides should be long-lasting. We tested the DNA hairpin-loop after long storage and also in the presence of semen — a critical parameter for a useful microbicide. At the Heinrich Pette Institute for Experimental Virology in Hamburg we placed a little container at the men’s room asking for anonymous “donation” of semen. That worked out perfectly — but when we submitted the manuscript we were asked immediately before they even processed it for the written consent of the donors, including their names and in addition the written approval by the Ethics Committee at the Hospital — this took weeks. Such requests are totally new. (Even the donor of a feces sample for feces transfer, described below, was required retrospectively to submit written consent.) Thus: No body fluid can be taken from anybody without written consent — no tears or a drop of urine — because genes in the fluid may indeed be sequenced and reveal a lot of personal information.
What next? A bottleneck is the high-quality production of the DNA hairpin, according to Good Manufacturing Practice (GMP). This is almost impossible to pay for. I went to Russia, twice to China, once to Africa. HIV is still a taboo subject, and the outrageously expensive GMP production is required (even if I find it in some cases unnecessary) — no short-cut is allowed in the Third World, and one can even risk going to jail. During my visit to China the head of the admission committee was sentenced to death and shot for insufficiently strict obedience to the Chinese rules, which Western companies often try to circumvent by going to China. His organs may have saved some lives.
The origin and future of HIV
It is surprising, that one of the most recent new results on HIV refer to its origin. Some time ago a committee analyzed the possibility that HIV was caused by a contaminated polio vaccine. It was “most likely not” caused by an HIV contamination of the polio vaccine produced in monkey cells.
An extensive sequencing analysis of hundreds of samples from patients in Kinshasa all the way back to the 1920s was performed only recently. One strain HIV-1 (M is the major strain) can be traced back to 1900 and another one (O) to 1920 in Congo, which increased in 1960 with unexpected speed in Kinshasa. Were hospitals treating hepatitis B, HBV and sexually transmitted diseases short of sterile needles? Social and political changes and in the 1920s, the train system to the north and south-east of the then Congo State may have supported spreading of HIV. AIDS is the result of four independent viral cross-species transmissions from non-human primates to humans, two times from chimpanzees (M and N) and two times from gorillas (O and P) as judged from more than 6000 monkey feces samples collected in the wild. Subgroup O infection was observed in 1964 in a Norwegian sailor thought to be the “first” case. The O and P strains clustered in the Cameroon, 1000 km away from Kinshasa. The Congo River to Kinshasa served for transport of goods and people — and may have helped spread of the virus.
Only HIV-1 group M out of the four went global and became pandemic. It was transported by Haitian refugees who returned home from Kinshasa to Haiti, then the virus spread to San Francisco and to the rest of the whole world. Other strains clustered in Africa (group C), and Russia (group A), which are due to singular “founder effects”, transmission from a single person causing local spreads. HIV-2 can be traced back to 1940 and further to 1985 and has undergone 9 independent primate-to-human infections, but never did spread. HIV is thus clearly caused by contact with primates, — this is worrying because 80% of the people there still consume bushmeat — 20% of which is HIV-contaminated today in the Democratic Republic of Congo, DRC. Individual new infections have already been monitored, continuing the alphabet of the various groups. We do not know what made only one of the strains, M, pandemic! A specialist on this topic, Martine Peeters from Montpellier, answered: many parameters just coincided and caused the pandemic.
What about the future of HIV? HIV/AIDS is not primarily a problem for research any more. It is the best-studied virus of all. “Ending HIV/ AIDS” was the motto by Toni Fauci, Head of Infectious Diseases at the NIH already in 2012. A colleague stated “I’d rather get HIV than diabetes” (not me — to be honest). A major goal is to identify persons who are newly infected, so that they can be treated early, when they are most infectious. “Therapy as prevention” is an important achievement and will help until one day (perhaps) a vaccine arrives.
A surprising effect of HIV is the appearance of late-stage cancer. Three cancers are at the center of attention: lymphomas, cervical cancers and Kaposi sarcomas (KS). These cancers arise by synergism between HIV and other viruses such as the papilloma and herpes viruses. HIV itself is not an oncogenic virus. It has a relative, the human T-cell leukemia virus, HTLV-1, which is oncogenic and endemic in Japan, where it can cause fulminant leukemias. (It can be prevented by avoiding breastfeeding.) Retroviruses were the basis for cancer research and still belong close to one another. Their “teaching effect” for human cancer researchers has been enormous and will be discussed below in the context of oncogenes. Today, there is a new research institute founded under the direction of Harold Varmus, who won the Nobel Prize for the analysis of the first retroviral oncogene Src. Why HIV patients develop cancer, in spite of therapies and at least partial restoration of their immune systems, is one of the questions. Are there general defects, which could help us to understand the effect of the immune system on cancer development? The incidence of cancer increases with age, even in the absence of an immune-suppressing virus such as HIV. It is faster in HIV patients in spite of therapies — why?
In Russia I participated in a congress on HIV, and the two hepatitis viruses HCV and HBV (2013), supported by the U.S. health organization NIH with sessions about diagnostics and therapy in addition to science. Bureaucracy, regulatory affairs in respect of HIV/AIDS and tuberculosis, inter alia in Russian prisons. Tuberculosis is often a secret surrogate description for HIV/AIDS, which it is not socially acceptable to mention. In spite of a simultaneous translation system and announcements of English talks, there was no translator. When I finally found one, he refused to translate the session. This made my trip redundant. I wanted to understand the system and find the people in charge of a putative microbicide. No way.
Instead, I interviewed students at the reception and at some industry exhibitions who knew some English. Nobody visited them — no free pencils or other little presents? No interest? Not affordable anyway? The prices of therapeutics were skyrocketing. Western standards. One person had been in Kiel and spoke German, another spoke English. No, we do not know anything about HIV/AIDS. Condoms were once discussed several years ago, but people were too ashamed to buy them; homosexuality is a forbidden topic, as of course were drugs. No, my 14-year-old daughter does not know about HIV. HIV-infected individuals have to go “home” to their place of birth. Therapy is almost non-existent. “I love my country” was a repeated sentence in between — to please any spies who might have been in earshot? She preferred to go outside of the building. Until 20 years ago the health-care system was free — but no more. Not only in Russia, but also in China and India, people need more information, diagnostics, and therapies.
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