A glimpse into the world of human viruses by Hildegard Uecker and Barbora Trubenová January 25, 2019 It is a matter of opinion, or of definition, host cell. Finally, viruses need to spread from whether viruses are considered living cell to cell within an organism and from one organisms or peculiar chemical substances. organism to another, i.e. from the cells of one Theodosius Dobzhansky organism to the cells of another organism (see iruses are tiny biological agents that the box on viral transmission below). possess a genome but cannot repli- We are all infected by viruses. However, V cate on their own. In order to repli- luckily, many of them do not cause symptoms cate, they need to infect host cells and hi- and remain unnoticed. They may have neg- jack the host’s machinery. Therefore, one ative long-term effects, be entirely harmless, can argue that they are not really living or even provide benefits — it’s often hard to organisms. Alive or not, viruses are very know. We only notice viruses when they cause successful at tricking and hijacking cells. diseases. There are an estimated 1031 viruses on this planet, which infect all forms of life. They play an important role in many ecosys- tems and shape life on earth. In this issue, we will have a look at viruses that infect Fig. 1: Colorized transmission electron mi- humans. But don’t forget—no form of life croscopic images of the virions of measles, in- is safe. fluenza, and HIV (from left to right).a Viruses are classified as “DNA viruses” and “RNA viruses” depending on how their genetic aImages: (1) CDC/Cynthia S. Goldsmith; William material is stored (either as DNA or as RNA, Bellini, Ph.D. (2) National Institute of Allergy and In- respectively). About 70% of all viruses are fectious Diseases (3) CDC/A. Harrison; Dr. P. Feorino. RNA viruses. As you already know, RNA is less stable than DNA and RNA replication is more prone to errors. Thus, RNA viruses have Viral diseases a higher mutation rate than DNA viruses. Viruses are responsible for many human dis- Outside of host cells, the genetic material eases, including the common cold, influenza, of a virus is packed within the capsid, a shell measles, chickenpox, rubella, hepatitis, AIDS, of proteins. The entire unit (genetic material Ebola, Zika, and others. Some viruses can and capsid) is called a virion. When a virus even cause cancer (Peyton Rous was awarded infects a host cell, the viral DNA or RNA is the 1966 Nobel prize in Medicine for this dis- released from the capsid into the cell, where covery). it is replicated by the molecular tools of the A glimpse into the world of human viruses Page 2 Viral transmission: How do viruses spread? Viruses can pass to new cells in two ways, this strategy are called retroviruses. Upon either horizontally or vertically. infection of a cell, they reverse-transcribe Horizontal transmission denotes the their RNA into DNA. This is very unusual— spread of the virus from an infected to as you learned in a previous issue, the an uninfected cell of the same generation. process normally goes in the other direc- tion. The viral DNA is then integrated somewhere in the genome of the host cell. You will learn more about an important retrovirus—the HIV virus—below. Transmission between individuals can In order for horizontal transmission to take occur either horizontally or vertically. Hor- place, new virions must be produced. To izontal transmission between different indi- do this, the virus makes use of the molec- viduals can, for example, happen through ular machinery of the host cell to build free virions in saliva droplets. Other a capsid and assemble the virion. Then, viruses use vectors—some outside agent— to reach uninfected cells, the new virions to spread from one individual to another. are usually released into the liquid sur- For instance, most plant viruses use insects rounding the cell. This release can hap- to get from one plant to another. Vertical pen all at once, in a process that kills the transmission is, for instance, possible from host cell, or more gradually, in a way that the mother to the fetus. This happens with leaves the host cell intact. Free virions can- the rubella virus, the cause of German not move by themselves. Rather, they rely measles. Normally, German measles is not on luck—on random encounters with new a serious disease. However, if a pregnant host cells. Virions can also reach uninfected woman passes the virus to her child, this cells through cell-to-cell spread—in this pro- can cause serious harm to the child’s health. cess, virions pass directly from an infected Furthermore, viruses can be passed on to to an uninfected adjacent cell without pass- the next generation by infecting cells of the ing through any liquid. This direct trans- germ line (egg/sperm). Viruses that are mission is conducive to viral spread within transmitted via the germline are usually an organism, because it is fast and helps not very harmful to their host—otherwise, the virus escape the individual’s immune they would compromise their own survival. system. We will talk more about such transmission With vertical transmission, the virus and its consequences later. is passed on from the mother cells to the daughter cells during cell division. Some viruses in- corporate their genetic material into the host genome, so it gets replicated to- gether with the host DNA. RNA viruses that use A glimpse into the world of human viruses Page 3 Most (if not all) human viruses derive from infection occurs—respond and produce new animal viruses. For example, the measles tools tailored to fighting the specific virus that virus most likely evolved from (an ancestor is attacking (however, some viruses manage of) rinderpest, a virus that infects cattle. Nor- to hide from our immune system). mally, viruses that are well-adapted to an an- One of these tools is antibodies. The pro- imal host are not well-adapted to humans. duction of antibodies is triggered by surface This happens because viruses need to inter- proteins of the virion (proteins belonging act with many of their host’s proteins to com- to the capsid or to an envelope that covers plete their life cycle. These proteins are not al- the capsid). Substances that trigger an im- ways identical in animals and humans, which mune response are called antigens (antigen means the viral tools cannot be used on the hu- = antibody generator). The antibodies pro- man version of a protein. However, if the virus duced by the immune cells inactivate the virus is not entirely unfit in the new environment by binding to these antigens. Antibodies are of the human body and also has some chance antigen-specific, i.e. they can only bind to the to spread from human to human, it might antigens they are designed for (see extra-box accumulate adaptive mutations and evolve at the end of the article). Another tool to fight into a well-adapted human pathogen. This viruses are killer T-cells that circulate through transition is facilitated through close contact the body to find and kill infected cells. Killer between animals and humans (providing the T-cells recognise infected cells from the viral virus with many chances to infect humans) antigens present on their surfaces. However, and large, dense communities (allowing the just like antibodies, killer T-cells are antigen- virus to spread between humans more eas- specific, and infection by a particular virus ily). The emergence of new human viruses triggers the production of specialised killer from animal viruses is hence often associated T-cells that can act against it. Following an with changes in human lifestyle. For example, infection, we keep producing the specific an- the evolution of the measles virus is hypothe- tibodies and killer T-cells for decades.1 sised to have occurred 3000-2500 BC, when If a virus gains mutations that alter its anti- humans in the Middle East started to keep gens, the old antibodies and killer T-cells will livestock and to live in large communities. not work anymore, and our immune system (However, other researchers think measles must produce new, suitable ones to fight the originated much later, in the 11th or 12th evolved virus. There is great variation in the century.) patterns of antigenic evolution across viruses. Even after the successful transition from Some viruses evolve antigenic changes very an animal to a human pathogen, viruses con- slowly. Once we have manufactured the an- tinue to be challenged by the human immune tibodies (and other tools) to fight them, we system. On one hand, the genes coding for the are immune for the rest of our lives, since the components of our immune system can evolve virus does not change a lot over the course through mutation and recombination, bring- of decades—for some, we do not observe any ing about variants that are better at fighting antigenic evolution at all. An example is the common pathogens. This is a process hap- measles virus. Other viruses change more pening across human generations. On the quickly. While they might not escape the im- other hand, the immune system of a single mune system during the course of infection, a person itself is adaptive and can—once an slightly changed variant might come back one 1Our immune system has many further components. In particular, it also has non-adaptive parts that act rapidly and are not specific to a given pathogen. E.g. we also have natural killer cells that are not antigen-specific and constantly “patrol” in our body to kill infected cells as a quick first response to invading pathogens.