New research from Stockholm University and Karolinska Institutet shows that viruses interact with proteins in the biological fluids of their host which results in a layer of proteins on the viral surface.
This coat of proteins makes the virus more infectious and facilitates the formation of plaques characteristic of neurodegenerative diseases such as Alzheimer’s disease.
Are viruses dead or alive? Well… both.
Viruses can only reproduce inside living cells and exploit the cellular machinery of their host to their benefit.
A virus is a small parasite that cannot reproduce by itself. Once it infects a susceptible cell, however, a virus can direct the cell machinery to produce more viruses. Most viruses have either RNA or DNA as their genetic material.
The nucleic acid may be single- or double-stranded.
The simplest viruses contain only enough RNA or DNA to encode four proteins.
The most complex can encode 100 – 200 proteins.
The study of plant viruses inspired some of the first experiments in molecular biology. In 1935, Wendell Stanley purified and partly crystallized tobacco mosaic virus (TMV); other plant viruses were crystallized soon thereafter.
Pure proteins had been crystallized only a short time before Stanley’s work, and it was considered very surprising at the time that a replicating organism could be crystallized.
A wealth of subsequent research with bacterial viruses and animal viruses has provided detailed understanding of viral structure, and virus-infected cells have proved extremely useful as model systems for the study of basic aspects of cell biology.
In many cases, DNA viruses utilize cellular enzymes for synthesis of their DNA genomes and mRNAs; all viruses utilize normal cellular ribosomes, tRNAs, and translationfactors for synthesis of their proteins.
Most viruses comman-deer the cellular machinery for macromolecular synthesis during the late phase of infection, directing it to synthesize large amounts of a small number of viral mRNAs and proteins instead of the thousands of normal cellular macromolecules.
For instance, animal cells infected by influenza or vesicular stomatitis virus synthesize only one or two types of glycoproteins, which are encoded by viral genes, whereas uninfected cells produce hundreds of glycoproteins.
Such virus-infected cells have been used extensively in studies on synthesis of cell-surface glycoproteins.
Similarly, much information about the mechanism of DNA replication has come from studies with bacterial cells and animal cells infected with simple DNA viruses, since these viruses depend almost entirely on cellular proteins to replicate their DNA.
Viruses also often express proteins that modify host-cell processes so as to maximize viral replication.
For example, the roles of certain cellular factors in initiation of protein synthesis were revealed because viral proteins interrupt their action.
Finally, when certain genes carried by cancer-causing viruses integrate into chromosomes of a normal animal cell, the normal cell can be converted to a cancer cell.
Since many viruses can infect a large number of different cell types, genetically modified viruses often are used to carry foreign DNA into a cell.
This approach provides the basis for a growing list of experimental gene therapy treatments. Because of the extensive use of viruses in cell biology research and their potential as therapeutic agents, we describe the basic aspects of viral structure and function in this section.
- Viruses are intracellular parasites that replicate only after infecting specific host cells. Viral infection begins when proteins on the surface of a virion bind to specific receptor proteins on the surface of host cells. The specificity of this interaction determines the host range of a virus.
- Aside from being the causative agents of many diseases, viruses are important tools in cell biology research, particularly in studies on macromolecular synthesis (see Table 6-3).
- Viruses can be counted and cloned by the plaque assay (see Figure 6-14). All the virions in a single plaque compose a clone derived from the single parental virion that infected the first cell at the center of the plaque.
- Individual viral particles (virions) generally contain either an RNA or a DNA genome, surrounded by multiple copies of one or a small number of coat proteins, forming the nucleocapsid. The nucleocapsid of many animal viruses is surrounded by a phospholipid bilayer, or envelope.
- During lytic replication, host-cell ribosomes and enzymes are used to express viral proteins, which then replicate the viral genome and package it into viral coats. The multiple progeny virions produced within a single infected cell eventually are released, following cell lysis or gradual disintegration of the cell (see Figure 6-16). Progeny nucleocapsids of enveloped viruses are released by budding of the host-cell membrane in which viral membrane proteins have been deposited (see Figure 6-17).
- Some bacterial viruses (bacteriophages) may undergo lysogeny following infection of host cells. In this case, the viral genome is integrated into host-cell chromosomes, forming a prophage that is replicated along with the host genome. When suitably activated, a prophage enters the lytic cycle (see Figure 6-19).
- All retroviruses and some other animal viruses can integrate their genomes into host-cell chromosomes (see Figure 6-22). In some cases, this leads to abnormal cell replication and the eventual development of cancers.
- Recombinant viruses can be used as vectors to carry (transduce) selected genes into cells. In this approach, viral genes required for the lytic cycle are replaced by other genes. The use of viral vectors for gene therapy is still in its infancy, but has great potential for treatment of various diseases.
However, before entering a host cell, viruses are just nanometer-sized particles, very similar to artificial nanoparticles used in medical applications for diagnosis and therapy.
Scientists from Stockholm University and Karolinska Institutet have found that viruses and nanoparticles share another important property: they both become covered by a layer of proteins when they encounter the biological fluids of their host before they find their target cell.
This layer of proteins on the surface influence their biological activity significantly.
“Imagine a tennis ball falling into a bowl of milk and cereal.
The ball is immediately covered by the sticky particles in the mix and they remain on the ball when you take it out of the bowl.
The same thing happens when a virus gets in contact with blood or lung fluids that contain thousands of proteins.
Many of these proteins immediately stick to the viral surface, forming a so-called protein corona,” Kariem Ezzat of Stockholm University and Karolinska Institutet explains.
Kariem Ezzat and his colleagues studied the protein corona of respiratory syncytial virus (RSV) in different biological fluids. RSV is the most common cause of acute lower respiratory tract infections in young children worldwide, leading up to 34 million cases and 196,000 fatalities each year.
“The protein corona signature of RSV in the blood is very different from that in lung fluids.
It is also different between humans and other species, such as rhesus macaque monkeys, which also can be infected with RSV,” Ezzat says.
“The virus remains unchanged on the genetic level.
It just acquires different identities by accumulating different protein coronae on its surface depending on its environment.
This makes it possible for the virus to use extracellular host factors for its benefit, and we’ve shown that many of these different coronae make RSV more infectious.”
The researchers from Stockholm University and Karolinska Institutet have also found that viruses such as RSV and herpes simplex virus type 1 (HSV-1) can bind a special class of proteins called amyloid proteins.
Amyloid proteins aggregate into plaques that play a part in Alzheimer’s disease where they lead to neuronal cell death.
The mechanism behind the connection between viruses and amyloid plaques has been hard to find till now, but Ezzat and his colleagues found that HSV-1 is able to accelerate the transformation of soluble amyloid proteins into thread-like structures that constitute the amyloid plaques.
In animal models of Alzheimer’s disease, they saw that mice developed the disease within 48 hours of infection in the brain.
In absence of an HSV-1 infection, the process normally takes several months.
“The novel mechanisms described in our paper can have an impact not only on understanding new factors determining how infectious a virus is, but also on devising new ways to design vaccines.
In addition, describing a physical mechanism that links viral and amyloid causes of disease adds weight to the increasing research interest in the role of microbes in neurodegenerative disorders such as Alzheimer’s disease and opens up new avenues for treatments,” Ezzat says.
More information: Kariem Ezzat et al. The viral protein corona directs viral pathogenesis and amyloid aggregation, Nature Communications(2019). DOI: 10.1038/s41467-019-10192-2
Journal information: Nature Communications
Provided by Stockholm University