A2.3 Viruses

Viruses are not cells. A virus particle outside a host is inert: it does not feed, respire, excrete or grow. It can only reproduce after it has entered a living cell, so every virus is an obligate intracellular parasite. Because viruses are so diverse, very few features are found in all of them. Compare them with the structure of cells in A2.2 Cell structure.

The features every virus has

• Small size. Most viruses are between about 20 and 300 nm across, smaller than almost all bacteria and far smaller than plant or animal cells. A virus has to be small enough to enter its host cell.
• Fixed size. Viruses do not grow. A new virus is put together inside a host cell from ready-made parts, a fixed number of each, so it has its full size as soon as assembly is complete.
• Nucleic acid as genetic material. The genome is made of either DNA or RNA, never both. The genome is small, often only a handful of genes.
• A capsid made of protein. The nucleic acid is enclosed in a protein coat, the capsid. It is built from many copies of one or a few kinds of protein subunit, which self-assemble into a symmetrical structure such as an icosahedron or a helix. Repeating subunits mean only a few genes are needed for the whole coat.
• No cytoplasm. There are no ribosomes, no organelles and no metabolism inside a virus.
• Few or no enzymes. Viruses use the enzymes of the host cell. The few they carry are needed to copy their genetic material or to infect the host: HIV carries reverse transcriptase and integrase. The lambda particle carries no enzymes at all: it uses the host’s DNA and RNA polymerases, although its genome codes for a few proteins of its own, such as integrase.

Beyond those shared features, viruses vary enormously.

• Genetic material: DNA or RNA (see A1.2 Nucleic acids), which may be single-stranded or double-stranded, linear or circular, in one molecule or in several separate segments.
• Shape: capsids may be icosahedral, helical (rod-shaped) or more complex, like the head-and-tail structure of many bacteriophages.
• Envelope: some viruses are enveloped: as new particles bud through one of the host cell’s membranes, they become wrapped in a lipid bilayer taken from it, with glycoproteins coded for by the virus embedded in it. Others are non-enveloped, and their capsid is their outer surface.

Single-stranded DNA viruses complete the set, for example the parvoviruses of animals and phage φX174, which infects E. coli. So between them, viruses use all four combinations of DNA or RNA, single- or double-stranded. Sizes range from under 20 nm to giant viruses such as mimivirus, which are larger than some bacteria.

A virus cannot make ATP, take in nutrients or make proteins, so it relies on a host cell: it uses the host’s ATP, nucleotides, amino acids and ribosomes. In the lytic cycle the virus uses the host’s machinery to make many copies of itself and then destroys the cell.

Stages in lambda

1. Attachment. The tail fibre binds to a specific receptor protein, LamB, in the outer membrane of E. coli. Binding is specific, so lambda infects only bacteria that carry this receptor.
2. Injection. The linear DNA is injected through the tail into the cytoplasm; the empty capsid stays outside. The two ends of the DNA are short complementary single-stranded sections, so they pair up by complementary base pairing and the DNA becomes a circle.
3. Replication and synthesis. Viral genes are transcribed by the host’s RNA polymerase and the mRNA is translated by host ribosomes (D1.2 Protein synthesis), using host ATP, nucleotides and amino acids. The viral DNA is replicated many times, and large amounts of head and tail proteins are made.
4. Assembly. Capsid proteins self-assemble into heads, each head is filled with one copy of the DNA, and tails are attached.
5. Lysis. Viral enzymes made late in the cycle break down the cell wall from inside. The cell bursts and dies, releasing around 100 new phages, which can each infect another cell.

The whole cycle takes about an hour in good conditions, so numbers of phages can rise extremely fast.

After injection, lambda’s DNA does not always enter the lytic cycle. It can instead follow the lysogenic cycle, shown in the last three steps of the animation. Phages that can do this are called temperate phages. Lysogeny is more likely, for example, when many phages infect the same cell or when the host is short of nutrients.

Stages

1. Attachment and injection happen exactly as in the lytic cycle, and the DNA circularizes.
2. Integration. A viral enzyme, integrase, inserts the circular viral DNA into the host chromosome at a particular site. The integrated viral DNA is now called a prophage, and the bacterium is a lysogen.
3. Repression. A viral repressor protein binds to the prophage and switches off the genes needed for the lytic cycle, so no viral proteins for new phages are made and the host is not harmed.
4. Replication with the host. Every time the bacterium replicates its chromosome before binary fission, the prophage is replicated with it, so both daughter cells inherit it. A whole population of lysogens can grow from one infected cell.
5. Induction. Stress such as DNA damage by UV light or certain chemicals inactivates the repressor. The prophage is cut out of the chromosome and enters the lytic cycle, so the cell is eventually lysed.

Living organisms share many features, such as ribosomes, a plasma membrane and core metabolic pathways, because they inherited them from a common ancestor. Viruses are different: no single gene is found in all viruses, and their genomes and ways of replicating vary widely. This suggests that viruses are not one natural group (clade) but arose several times, from different sources.

Why viruses share some features anyway

All viruses live as extreme obligate parasites. Any genetic element that is transferred between host cells faces the same problems: it must be small enough to enter a cell, protected in transit, and able to use the host’s machinery. A protein capsid, small size and the loss of metabolism are good solutions to these problems, so the features viruses share may be the result of convergent evolution rather than common ancestry. Compare the streamlined body shapes of sharks and dolphins, which evolved separately in response to the same demands of fast swimming.

The genetic code

Viruses use the same genetic code as living organisms. This is essential, because viral proteins are made by the host’s ribosomes and tRNA. It is taken as evidence that viruses evolved after the genetic code was established in cells, probably from cellular genetic material, rather than before cells existed.

Hypotheses for the origin of viruses

• The escape hypothesis fits the similarity between some viruses and mobile genetic elements such as plasmids and transposons.
• The reduction hypothesis fits the giant viruses, whose large genomes include genes once thought to be found only in cells. It also mirrors what is seen in some parasitic bacteria, which have lost many genes.
• The virus-first hypothesis conflicts with the fact that all known viruses depend on cells.

Some viruses, especially RNA viruses and retroviruses, evolve far faster than any cellular organism. The reasons are:

• High mutation rates. Most RNA viruses copy their genomes with RNA-dependent RNA polymerases, and retroviruses with reverse transcriptase. These enzymes do not proofread, so copying errors are not corrected. DNA viruses that use proofreading polymerases mutate far more slowly. (Coronaviruses are an exception among RNA viruses: they have a proofreading enzyme, so they mutate more slowly than influenza or HIV.)
• Short generation times. A replication cycle takes hours rather than years, and only about an hour for lambda.
• Huge numbers of offspring. One infected person can produce billions of new virus particles a day, so even rare mutations appear constantly.
• Mixing of genomes, by recombination or by reassortment of genome segments.
• Strong selection by the host’s immune system and by antiviral drugs, which favours any variant they no longer act on.

Influenza viruses

Influenza viruses have eight separate RNA segments and an error-prone polymerase.

• Antigenic drift: point mutations gradually change the surface glycoproteins haemagglutinin (HA) and neuraminidase (NA), so antibodies made after earlier infections or vaccination bind less well. The vaccine therefore has to be updated every year to match the strains expected to circulate.
• Antigenic shift: when two different strains (for example a human and a bird strain) infect the same cell, their segments can be mixed into new combinations (reassortment). The result may be a subtype to which almost nobody is immune, as in the 1957 and 1968 pandemics.

Resistance to antiviral drugs also spreads: most influenza A viruses are now resistant to the older drug amantadine.

HIV

HIV’s reverse transcriptase makes many errors, and recombination between the two RNA copies adds more variation. Within one infected person, the virus soon becomes a population of genetically different variants. As a result:

• the immune system cannot clear the infection, because new variants keep escaping the antibodies and T cells made against earlier ones;
• resistance to any single drug evolves quickly, so patients take a combination of antiretroviral drugs acting on different targets. A variant resistant to all of them at once is very unlikely to arise;
• no effective vaccine has yet been developed, and infection is managed lifelong rather than cured.

Viruses are also attacked by the body’s defences described in C3.2 Defence against disease.