Single-stranded RNA virus review

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I enter the nerves of the diseased and cause inflammation of the brain in humans and other animals. I am present in more than 150 countries, with more than 3 billion people in regions of the world living where I exist. In 2015 alone, I caused about 17,400 deaths. I am the rabies virus. I belong to the Lyssavirus genus, which is composed of RNA viruses in the family Rhabdoviridae, order Mononegavirales.

Like other lyssaviruses, I have a single-stranded RNA genome with negative sense. I have two major structural components: a helical ribonucleoprotein core (RNP) and a surrounding envelope. In my RNP, my genomic RNA is tightly encased by the nucleoprotein. My RNA genome encodes the five genes: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA polymerase (L). The order of my five genes is highly conserved. My glycoprotein forms approximately 400 trimeric spikes which are tightly arranged on my surface. My matrix protein is associated both with the envelope and the RNP and may be the central protein of rhabdovirus assembly. In addition, like other lyssaviruses, I have a helical symmetry, giving me a cylindrical shape with a length of about 180 nm and a cross-sectional diameter of about 75 nm. One of my ends is rounded or conical and my other end is planar or concave. My lipoprotein envelope carries knob-like spikes composed of Glycoprotein G.

However, these spikes do not cover my planar end. Beneath my envelope is the membrane or matrix (M) protein layer which may be invaginated at the planar end. Once I am within a muscle or nerve cell, I undergo replication. The trimeric spikes on the exterior of my membrane interact with with a cell receptor, the most likely one being the acetylcholine receptor (an organic chemical that functions in the brain and body of many types of animals as a neurotransmitter). The cellular membrane then pinches in a procession known as pinocytosis and allows me to enter the cell by way of an endosome. Using the acidic environment of the endosome, I then bind to its membrane simultaneously, releasing my five proteins and single stranded RNA into the cytoplasm. The L protein that I released then transcribes five mRNA strands and a positive strand of RNA, which are all from my original negative strand RNA, using free nucleotides in the cytoplasm. The five mRNA strands are then translated into their corresponding porteins (P, L, N, G, and M proteins) that I hold at free ribosomes in the cytoplasm. Some of my proteins require post-translative modifications.

For example, my G protein travels through the rough endoplasmic reticulum, where it undergoes further folding, and is then transported to the Golgi apparatus, where a sugar group is added to it (glycosylation). Where there are enough proteins, my polymerase enzyme will begin to synthesize new negative strands of RNA from the template of the positive strand RNA. These negative strands will then form complexes with my N, P, L and M proteins and then travel to the inner membrane of the cell, where my G protein has embedded itself in the membrane. My G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle that I will also become. At this point, the virus then buds from the cell, making a duplicate of me. From the point of entry, I (a new version of myself as a virus) am neurotropic, traveling quickly along the neural pathways into the central nervous system. I usually first infect muscle cells close to the site of infection, where I am able to replicate without being ‘noticed’ by the host’s immune system. Once enough of me have been replicated, the replicates and I begin to bind to acetyl choline receptors (p75NR) at the neuromuscular junction. After doing so, we (all the replicated versions of me) then travel through the nerve cell axon via retrograde transport, as our P proteins interact with dyneins, which are proteins present in the cytoplasm of nerve cells. Once we reach the cell body we travel rapidly to the Central Nervous System (CNS), replicating in motor neurons and eventually reaching the brain.

After the brain is infected, the we travel centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where I (as the overall virus) am then ready to be transmitted to the next host. All warm-blooded species, including humans, have the possibility of becoming infected by me and of developing the symptoms. In addition, I have also been adapted to grow in cells of poikilothermic (“cold-blooded”) vertebrates. Most animals that are infected by me have the ability to transmit the disease to humans. Of all of the animals that pose the possibility of being infected, bats, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, dogs, mongooses and cats present the greatest risk to humans. Small rodents, such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, and lagomorphs such as rabbits and hares, are almost never infected by me, and thus are not known to transmit rabies to humans. I am usually present in the nerves and saliva of an animal that shows the signs of having rabies. Therefore, the route of infection is usually, but not always, by a bite. In many cases, the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior due to me modifying the behavior of the host in order to facilitate my transmission to other hosts. Transmission of me between humans is extremely rare, but a few cases have been recorded through transplant surgery.

During the stage when I travel to the nervous system of the host after a bite, the virus cannot be easily detected, and vaccination may still grant cell-mediated immunity to prevent the onset of rabies. However, after I reach the brain, I rapidly causes encephalitis, or inflammation of the brain due to infection. This is the stage when symptoms begin. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Symptoms in humans typically appear one to three months after I cause infection; however, this time period can vary from less than one week to more than one year. The time is dependent on the distance I must travel along nerves to reach the central nervous system. Early symptoms may include fever and tingling at the site of exposure, which is then followed by slight or partial paralysis, terror, abnormal behavior, confusion, anxiety, paranoia, agitation, insomnia and hallucinations that progresses to delirium and a coma. During the later stages of my infection, any mammal infected may also demonstrate hydrophobia ( “fear of water”). When experiencing hydrophobia, symptoms include showing showing panic when presented with liquids to drink, has difficulty swallowing, and cannot quench his or her thirst. When experiencing hydrophobia, saliva production on is greatly increased, and attempts to drink, or even the suggestion of drinking, can cause excruciatingly painful spasms of the muscles in the throat and larynx.

The reason for the reflex against water is to encourage my transmission, for the salivary glands of the infected individual being the location where I multiply and assimilate. The ability for me to transmit would decrease significantly if the infected individual could swallow saliva and water. Death due to me usually occurs two to ten days after the first symptoms appear. Once symptoms are presented, survival is rare, even with the administration of proper and intensive care. Jeanna Giese, who in 2004 was the first patient treated with the Milwaukee protocol, became the first person ever recorded to have survived a rabies infection caused by me without receiving successful post-exposure prophylaxis. An intention-to-treat analysis has since found this protocol has a survival rate of about 8%.

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