A virus is a small infectious particle that hijacks the machinery and the metabolism of our cells to grow and to reproduce.
Each viral particle, or virion, consists of nucleic acis. These acids include either DNA as deoxyribonucleic acid or RNA as ribonucleic acid is single and in double-stranded form. The acids are enclosed by a capsid. They are made from monomers known as nucleotides. Every nucleotide consists of three components: a 5-carbon sugar, a phosphate group, and a nitrogenous base. If the sugar is deoxyribose, the polymer is DNA.
In most viruses, the neuclear capside is enclosed by an outer envelope. Influenza type A (an envelope of single-stranded RNA virus) has been widely studied and serves in the video shown to illustrate the life cycle of one common virus.
Scientists believe that Influenza Virus is spread from person-to-person through exposure to large respiratory droplets, direct contact or airborne dispersal. Infection takes place mainly in the respiratory tract. Infection begins with the attachment of virus proteins to a receptor on the surface of the host’s cell. The virus is then taken into the cell by Receptor-mediated endocytosis. Receptor-mediated endocytosis, also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, other proteins – and in some cases viruses – by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being absorbed.
As the virus enters the cell, the virus is internalised in a membrane-bound capture vesicle (Small, membrane-bounded, spherical organelle in the cytoplasm of a eucaryotic cell) that carries the viral core. The vesicle is transported along microtubules inside the cell (Microtubules are conveyer belts inside the cells. They move vesicles, granules, organelles like mitochondria, and chromosomes via special attachment proteins. They also serve a cytoskeletal role. Structurally, they are linear polymers of tubulin which is a globular protein).
During transport, the membrane of the vesicle fuses with the membrane of the virus and the capsid undergoes uncoding. The viral core RNA and proteins are then released into the cytoplasm where they are guided by post proteins to the nucleus of the host’s cell. At the nuclear membrane, the viral core uses post protein channels to enter. Inside the nucleus, cell machinery is utilised by the virus to replicate the viral genome and make Messenger RNA. Messenger RNA (mRNA) is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression. Some viral mRNA exits the nucleus to exploit cellular ribosomes – the direct synthesis of viral proteins. Viral proteins go back to the nucleus to associate with viral RNA. These nuclear proteins again leave the nucleus and use cellular processes to travel to the cell surface. Viral surface proteins are made and processed in the cytoplasm and also travel to the cell surface where they combine with encapsulated nuclear proteins to forge viruses which depart from the cell and goes on to infect other cells. Due to the limited number of viral proteins and nuclear acids that can be targeted, the development of effective anti-viral agents is especially challenging. Drugs currently used in treating Influenza act by inhibiting viral proteins. However, these antiviral drugs are of limited effectiveness and, like antiviral drugs used to treat HIV and other viruses, are prone to development of viral resistance through mutation to avoid the interaction with the drug.
At present, vaccines to stimulate the production of anti-bodies against the virus and stimulate post cellular responses to injest the virus remain the best strategy for controlling certain viral diseases but they are of limited effectiveness against rapidly mutating viruses and they are ineffective against viruses that cause the common cold and AIDS.
Scientists are working on new and better ways to prevent and manage viral infection by developing a platform of post cell-based targets to inhibit viral replication. To find these targets, Zirus (the company who produced the video below) is using a patented technology called the ‘gene trap’. Scientists are transfecting each cell in a colony of identical cells with a retro-virus. A small particle which causes the random insertion into the cell’s DNA. The insertion randomly disrupts the function of a single gene in a cell into which it is inserted. Collectively, these cells create a unique library of cells each having a different single gene disrupted. Importantly, cells that require the disrupted gene to survive, will die and are not identified by the gene track. Thus, there is a selection against genes that are essential for cell survival and likely toxin if targeted with drugs. Scientists then infect every remaining cell with a virus that normally kills all cells and identify those cells that survive infection. Since all cells would normally have been killed by the virus, the surviving cells must have survived due to a gene disruption that the virus must use or hijack to replicate. these specifically identified genes, and their RNA proteins, when turned off, prevent a particular virus from replicating.
The ‘gene trap’ represents a cost-effective and efficient platform for the discovery of targets and drugs to block viral infection. Using this technique, we have efficiently discovered hundreds of human cellular targets essential for viral replication. Using these cellular targets, we then developed drugs that selectively blocked the function or production of the target gene properties. By inhibiting cellular proteins critical to the virus, we stopped the virus in its tracks and prevented it from growing and spreading. By blocking cellular targets, we can stop any type of virus from replicating. Significantly, many of our targets can be used to block many different types of viruses. For example, blocking a single gene target can block Ebola, HIV and Influenza.
Thus, by using an effective broad spectrum of anti-viral drugs, we can tackle and block viruses. Zirius is also applying its scientific endeavours to tackling multi drug-resistant bacteria as well as bacteria that are listed as bio-terrorism threats by the CDC and NIH. Whether made by nature or by mankind, there’s a positive future for reducing the threats caused by viruses.