Silent companions
"100 percent human"? No, we are not. In addition to countless microbial communities that help with digestion, for example, the human body harbors an abundance of viral mini-parasites. Although we usually don't notice them at all, the lodgers are by no means quiet.
Some just won't let go. Once herpesviruses or certain adenoviruses, parvoviruses, retroviruses or papillomaviruses have entered the human body, they can no longer be expelled. Either only their genetic material survives in the cells, or they hide in body tissues over a long period of time and get their hosts to produce virus building blocks or complete particles at the lowest level. Does that hurt or have people come to terms with their stowaways? You can't lump everyone together. But some silent companions are possibly more harmless than you think, while others are criminally underestimated.
Immortalized in the genome
Genetic researchers were surprised to discover a few years ago that the human genome is riddled with base sequences that are very similar to the genes of retroviruses. "Such sequences make up about eight percent of the human genome," says Jens Mayer, who researches endogenous retroviruses in the Human Genetics department at Saarland University in Homburg. Where do these viral genes come from in the human genome? They are probably the remnants of infections from a very long time ago. Back then, retroviruses had infected the germline cells and incorporated their genome – as so-called proviruses – into the DNA of our ancestors. A very smart move, because to this day we carry this information around with us.
Although the term "retrovirus" conjures up an uneasy connotation, research has yet to provide definitive evidence that human endogenous retroviruses, or HERV for short, cause disease. They are often genetically severely crippled, then consist only of defective control segments and can no longer produce virus products. Some of the still intact retroviral control segments even positively influence the activity of human genes. The digestive enzyme amylase, for example, is only produced in the salivary glands of the mouth because a HERV switching element that used to boost the production of viral proteins preceded the amylase gene a long time ago. "In contrast to other mammals, humans are therefore able to determine whether the food contains carbohydrates after chewing for a short time," explains Mayer. Amylase releases sugar from starch, the chyme tastes sweet.
Overall, HERVs have a neutral or more positive impact on humans
(Jens Mayer) However, some HERV sequences are translated into messenger RNA or even proteins and appear in both he althy and diseased body tissues. A protein from a provirus of the HERV-W family, syncytin, is even involved in the structure of the human placenta. Nevertheless, the suspicion is repeatedly voiced that HERVs are involved in the development of tumors or autoimmune diseases. In breast cancer, melanoma and testicular tumors, for example, there is always an increased production of protein structures of the HERV-K virus family. "When a testicular tumor is diagnosed, high antibody levels against these HERV proteins can be detected in the patient," says Mayer. Whether this observation is merely an accompanying phenomenon of tumorigenesis or has something to do with it remains to be clarified. "All in all, the HERVs have a neutral or rather positive influence on people," says the Homburg scientist.
Lots of tricks
Mini parasites from the herpes virus family are also very affectionate. In contrast to HERVs, however, humans are not usually born with them, but are mostly infected during childhood. Herpes viruses accompany people throughout their lives, but only come to light in very special situations. One of these silent companions is the cytomegalovirus (CMV). Although forty to one hundred percent of people carry this virus, depending on their age and geographic location, most don't even notice it. The body's defenses succeed in keeping the intruder in check, but not in driving out the virus once and for all. Because the CMV has a lot of tricks with which it can hide from the immune system in the host cells.
"The cytomegalovirus is an old companion of humans and perfectly adapted to them," explains Hartmut Hengel from the Institute of Virology at the Heinrich-Heine University in Düsseldorf. The doctor and his working group are trying to find out how the virus can outsmart the immune system and survive in various body tissues in a dormant state. Under normal conditions, at first glance this does not appear to be a problem for the organism. However, in situations where the immune system is weakened, CMV can become a real problem. Especially when the mother-to-be becomes infected during the second to sixth month of pregnancy and passes the virus on to the embryo, many of the children suffer permanent damage because the embryo's immune system is not yet fully developed.
The cytomegalovirus is an ancient companion of man and perfectly adapted to him
(Hartmut Hengel) The severe deformities caused by CMV are by no means rare. "Half of all pregnant women have never come into contact with the virus. If they become infected during pregnancy, it can be dangerous," explains Wolfgang Jilg, a member of the "Standing Vaccination Committee" (STIKO) and working at the University Hospital in Regensburg. It is estimated that one in every 1000 children is affected by CMV at birth, depending on region and population. CMV infections are also feared in people whose immune systems are temporarily or permanently weakened – patients who have had an organ transplant or those whose immune system has been paralyzed by AIDS.
To take action against CMV, antiviral agents are currently available, such as ganciclovir or valganciclovir, which is based on the same mechanism of action. However, both drugs have strong side effects and are therefore used for prophylaxis after transplantations, but not in pregnant women. A vaccination would be ideal for prevention.
Vaccinate against subtenants?
According to Jilg, there have been efforts for years to get their hands on an effective CMV vaccine - so far without any resounding success. This could possibly be reported soon from Hanover. The resident Vakzine Projekt Management GmbH (VPM) organizes the development of vaccines as part of an initiative of the BMBF and on behalf of the Society for Biotechnological Research in Braunschweig. VPM has the license for a promising CMV vaccine candidate, which is now to be prepared for human clinical trials in cooperation with a biotech company in Düsseldorf. "We expect that such tests will start next year," says Bernd Eisele, Head of Research and Development at VPM.
Only – who should be vaccinated? And how high would the public acceptance be? Eisele expects broad approval should a vaccine become available: "I expect a very high level of acceptance, similar to that which already exists with the rubella vaccination that is routinely used." While Eisele suggests vaccinating all children against CMV, according to STIKO member Jilg there is no classic reason to vaccinate everyone. The Düsseldorf CMV expert Hartmut Hengel also sees a valid justification for vaccination only for women who are CMV negative and who have never had contact with the virus and who are about to have an organ transplant.
Not an easy decision
The latest research work by immunologists has brought to light another reason to prevent an infection with CMV, possibly even in childhood, but also those with the Epstein-Barr virus (EBV). Graham Pawelec and his colleagues from the University Hospital in Tübingen are studying the immune system of older people. With increasing age, the immune system decreases for various reasons. Pawelec and his colleague Beatrix Grubeck-Loebenstein from the Institute for Biomedical Aging Research in Innsbruck have found that the permanent confrontation of the immune system with attached viruses promotes signs of wear and tear on the body's defenses. People whose immune systems have to constantly keep a CMV or EBV infection in check have fewer unused, fresh T cells in their blood than those who do not harbor these viruses. Older virus carriers can therefore no longer react as flexibly to new invaders, and the immune response - also to flu vaccinations - is significantly reduced.
Vaccinate – yes or no? There is no easy answer. In any case, a CMV vaccine together with therapeutic vaccines against diabetes or multiple sclerosis is at the top of the hit list of the American Institute of Medicine in Washington, which considers the urgency of new vaccines from a purely economic point of view.
