Reference no: EM13160675

Build a Virus Assignment

In order to build an unstable yet fatal virus, it is inevitable to choose a single-stranded RNA virus. Since mutation rate along with natural selection contributes to the evolution of viruses, virus with higher mutation rate is suitable. In comparison with DNA viruses, RNA viruses usually mutate more rapidly, because viral RNA polymerase does not have proofreading ability of DNA polymerase. This fabricated RNA virus is called SR077 virus. It replicates in a host cell by using reverse transcriptase to produce DNA from its RNA. If SR077virus exist, it would be one of the lethal viruses without any possible treatment or vaccines.

As an airborne virus, SR077 is transmitted by the respiratory tract. It can infect epithelium cells lining bronchus, alveolus as well as T cells. SR077 has a membrane that contains glycoproteins called frug, which binds to a proteinase-activated receptor (PAR)-2 of epithelium cells of bronchus and alveolar cells. SR077, also, contains spikes called frug17 that binds to cluster of differentiation 4 (CD4). After interaction between viral glycoproteins and receptors of a host cell, SR077 undergoes receptor-mediated endocytosis. It is internalized by both clathrin-mediated endocytosis in order to transport its genetic material across the cortex that supports plasma membrane of the host cell. The cortex is a network of actin fibers, motor proteins, membrane-linker proteins, and other components, which controls dynamic property of the plasma membrane. Virus-induced receptor mediated signaling causes reorganization of the cortex, easing its way in to a host cell. Then, internalized virus particles are captured by endosomes. Such acidic environment triggers the membrane fusion/penetration reactions that deliver the viral genetic material to the cytoplasm, where reverse transcription occurs.

Once SR077 is inside a host cell, it takes over the host’s genetic transcription machinery. Transcription is regulated by the transcription factors that can either active or repress the transcription of a gene. Both basal transcription factor II A (TFIIA) and transcription factor II B (TFIIB), which are necessary for RNA polymerase to function, are cleaved by the viral protease 5TEM. Moreover, the virus also affects elongation factor that regulates translation. elF4E binds to the 5’ cap of mRNA, while elF4G binds to poly A-binding protein, which binds to the poly A tail and activate the bound mRNA. However, these elF4 initiation factors interact with SR077 viral factors and inhibit the host translation. Complete inhibition of both transcription and translation of a host cell allows SR077 to replicate itself. SR077 contains a reverse transcriptase that frees the single-stranded RNA from the attached viral proteins and copies it into a complementary DNA (cDNA). Then, the cDNA is replicated and forms a weak bond with its complement. A double-stranded viral DNA is transported into the nucleus.

SR077 causes inhibition of nuclear import by degrading the nuclear pore complexes (NPCs). Usually, protein required for nuclear functions are transported from the cytoplasm into the nucleus through NPCs. NPCs are embedded in the double-membrane nuclear envelope and selectively transport in and out of nuclear proteins and RNAs. SR077 degrades two NPC components, Nup 153 and p62. Degradation of NPC components leads to accumulation of nuclear proteins in the cytoplasm. Due to the alteration done on NPCs, SR077’s double-stranded DNA, which is synthesized in the cytoplasm, import into the nucleus without nuclear localization signal (NLS). Once in the nucleus, the viral DNA is integrated into the host cell’s DNA by using integrase. Next, RNA is synthesized from the DNA and transport out of NPC without a nuclear export signal (NES). GTPase activating proteins (GAPs) hydrolyzes the Ran-GTP to Ran-GDP. This causes a conformational change and exportin release. SR077 degrades GAPs and blocks nuclear export of host proteins.

Apoptosis, also known as programmed cell death, is a normal occurrence in which organized sequence of events leads to the death of a cell. The internal stimuli, such as viral infection, trigger apoptosis by the intrinsic pathway of initiation. Internal cellular damage causes the proapoptotic Bcl-2 family members to become inserted into the outer membrane of mitochondria. Then, cytochrome c molecules are released from the intermembrane space of the mitochondria to the cytosol. In the cytosol, cytochrome c molecules form a multisubunit complex with Apaf-1 and procaspase-9 molecules.  As a result, the inhibiting domain of procaspase-9 is hydrolyzed and dissociated from the protein. Activated procaspase-9 cleaves additional caspases and destroys other proteins. SR077 triggers activation of ERk 1/2 and PKC that activate p90RSK. P90rSK activates CREB and induces the expression of Bcl-2 family. These Bcl-2 family members prevent cytochrome c to be released from the mitochondria, blocking activation of caspase-9.

In the secretory pathway, viral proteins are synthesized in the endoplasmic reticulum (ER) and transported to the Golgi complex where they are cleaved by furin resulting in the two SR077 envelop glycoproteins, frug and frug17. The secretory pathway begins as the secretory proteins, containing a signal sequence at their N-terminus, are directed to the ER. The signal sequence binds with a signal recognition particle (SRP), which stops translation until the SRP-ribosome complex binds to a SRP receptor (SR) in the ER membrane. Then, SRP is released and the ribosome attaches to the translocon. The signal sequence opens the translocon channel, which allows the protein chain to thread through the membrane and to release into the ER lumen. In the lumen of the ER, signal peptidase removes the signal peptide, and carbohydrates are added to the protein by oligosaccharyltransferase. After modification, most proteins that are soluble in the ER are transported in COP II-coated vesicles to the cis-Golgi. Then, the precursor glycoproteins are cleaved by furin, a cellular protease located in the trans-Golgi network. After packaging, the vesicles containing viral proteins bud off and move towards the plasma membrane, where frug and frug 17 anchor to the membrane of a host cell. Viral RNA and capsid proteins are gathered and pinched off of the infected cell membrane as a new virus.

Despite its ability to enter the cell, shutdown transcription and translation, inhibit nuclear import and export, prevent activation of apoptosis, and exit, SR077’s capability to mutate in a short period time differentiate itself from other viruses. This enables the SR077 to grow resistant to antiviral drugs. Also, the rapid mutation hinders the development of effective vaccines.  It is fortunate that such virus is only an imaginary one.