Exploration Of The Poliovirus Biology Essay

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As a child, I frequently traveled to my ancestral country of India. The first sensations that would hit me would be olfactory. The distinct smell of gasoline, pollution, and a hint of masala spices from street side vendors was always in the air. It is still hard to reproduce this smell anywhere else; evident by the luggage smell that brings me back whenever someone has traveled to India and has returned. Followed by the olfactory experience comes the visual. Stepping off the airport building in Mumbai, and walking onto the crowded inner city streets, I remember the beggars. Everyone from young to old suffer from poverty; from children carrying children, to the crippled elderly on the street. But the one thing that has been permanently grafted into my subconscious were the victims of Polio. Men, women, and children all showed the effects of the disease. Flaccid atrophied limbs usually immobilized them, and lack of government support meant that self-made contraptions were implemented to move about. I later learned that the Poliovirus is the causative agent of the disease depicted in the slums of India. This paper will explore this virus in depth, providing information on the structure of the virus, as well as a description of its properties. The life cycle will also be presented, focusing on specific strategies utilized for infection. Diseases caused by the virus will be surveyed, specifically focusing on the mechanisms of pathogenesis, as well as treatment and prevention strategies currently in use. Finally, the epidemiology of the diseases will be analyzed. The reasons as to its demographic and geographic locations, as well as economic and societal impacts in India will be investigated.

The poliovirus is from a family of viruses called Picornovirida. They are Baltimore class IV viruses and exhibit positive single-stranded RNA genome (1). Therefore, many properties of the poliovirus is characteristic for +ssRNA stranded viruses in general. The poliovirus is a non-enveloped virus, and this is characteristic for all Picornoviruses. The capsid of the poliovirus has a capsid that is shaped as a icosahedral and is symmetrical (1). This characteristic can be visualized when aggregates of the virus fit into a perfect crystal like lattice. It is also known that the capsid contains 60 units of capsid proteins, with each unit containing four proteins (1). A hallmark characteristic of the poliovirus capsid is the present of a groove that runs on each of the 12 corners of the icosahedral (1). The genome of the poliovirus is very small, and together with its simple capsid is considered one of the simplest of all viral forms. The genome is consisted of +ssRNA strands, and this property just like most +ssRNA viruses allow it to be used as messenger RNA. When in the cell, the genome can directly be translated into protein without the need for transcription, which is the case for -ssRNA viruses. The genome consists of one large open reading frame (ORF) which allows it to be translated continuously by ribosomes. (1) The benefits of this is that the small genome becomes even more efficient. Functionality is segregated by the cleavage patterns on the major protein produced, while the poly-protein is also able to have its own distinct functions. The genome itself has properties which include a 5'-UTR (untranslated region). This region contains a VPg (virus protein, genome linked), and a IRES (internal ribosome entry site) (2). The relevance of these regions on the genome will be discussed in the life cycle. The genome is separated by function. A total of ten mature polypeptides are able to be produced from the poly-protein, and the poly-protein contains three main cleavage intermediates (2). Some important proteins translated from this genome that plays a crucial role in the life cycle. VP1 proteins of the genome are capsid proteins, while VP2 and VP3 proteins are involved in cytopathic effects, proteases, and RNA synthesis. The capsid also contains signature glycoproteins that play a major role in attachment and entry.

The life cycle of the poliovirus starts with attachment on a cell. Since it is a non-enveloped virus, it will attach by capsid proteins on specific glycoprotein receptors of the cell. A important receptor that plays a crucial role for viral recognition is the glycoprotein CD155 (1). One advantage the poliovirus already has at this stage is the fact that this glycoprotein causes the poliovirus to exhibit many cell tropisms due to the fact that it is expressed on many different types of cells. Since the virus is only seen in humans and primates, this can mean important implications for study. The CD155 receptor are found on tissues present in the brain, spinal cord, leukocytes, lung, ileum, placenta, heart, skeletal muscle, kidney and liver, as well as other tissue epithelia (3). Previously it was briefly mentioned that one property of the poliovirus was the presence of deep grooves on each of its twelve capsid corners. The functional role this places in attachment is the fact that the CD155 glycoprotein will fit into this groove, and thus the capsid will adhere to the cell membrane (3). The process of entry for the poliovirus has been debated between receptor mediated endocytosis and injection. The method of endocytosis is still unclear however the injection mechanism has been elucidated. This involves capsid protein VP4, and VP1 (3). After receptor binding, a conformational change in these capsid proteins cause the creation of a pore in the cell membrane through which the +ssRNA is injected into the cell. In the endocytosis mechanism, the capsid triggers endocytosis by the cognate CD155 receptor interaction, and low pH will induce the same changes indicated in the injection mechanism. Once the +ssRNA is inside the cell, the VPg protein on the strand is first cleaved and then it is able to be translated by host ribosomes in the cytoplasm (1). The poliovirus uses its IRES for creating its own ribosomal binding site. This imitates the way the host cell conducts translation which is to circularize the RNA for continuous translation. The lack of a 5' cap is the main reason the host ribosome utilizes this binding site in the poliovirus genome (1). A important mechanism that should be pointed out is the lack of transcription factor eIF4E due to degradation by the poliovirus protease 3C, and in the same way, host TATA box binding proteins are cleaved to inhibit host transcription as well (1). This is very important for the poliovirus since it effectively silences the usage of host ribosomes for host mRNA translation. Once the poly-protein is formed, it is cleaved into smaller polypeptides, each with different roles such as protease for cleavage of host proteins and the poly-protein, RNA polymerase, VPg, ATPases, and caspid proteins. Just like all positive RNA viruses, replication is done by first transcribing the strand into negative RNA, and then transcribing the negative strand into positive strand RNA. The intermediate strand will involve a double stranded form of both positive and negative RNA.This is done in membrane-associated complexes involving the endoplasmic reticulum, and involves both viral proteins and host proteins (1). The reason for this may be to effectively sequesture all the proteins to a single location, so that replication can be fast and efficient. The VPg protein previously formed will serve as the primer on the positive strand. A unique mechanism in which the switch from translation of +ssRNA to transcription of +ssRNA occurs in the poliovirus lifecycle is the mechanism of circularizing the RNA using many RNA binding proteins. This will prevent the host ribosomes from entering the transcription complex (3). Assembly involves the capsid proteins called protomers coming together and forming a pentamer. Since the icosahedral contains 12 pentamers, these pentamers will come together and form the procapsid (1). The procapsid will encapsidate the newly replicated +ssRNA genome with the VPg protein attached. The virions exit the cell by lysis.

Cell function can be altered from infection by the inhibition mechanisms the poliovirus uses to silence the gene expression of the host. Another way cell function is altered in a infection is the inhibition of apoptosis by the L protein, but is usually counteracted by the host cell also trying to trigger apoptosis and limit viral spread (3). Cytopathic effects have been found to be nuclear condensation and distortion which visibly looks like nuclear blebbing due to membrane disruption (4). Also the vesicles in the cell start to loose their membrane stability and the membranes start to increase in permeability (4). This is due to the affects of the host cell in inducing apoptosis and thus prevents viral replication. The poliovirus is a fecal - oral virus, in which the common mode of entry into person is usually orally and shedding in the alimentary tract. The poliovirus is known to be asymptomatic or mild in a majority of cases, however 1% of cases result in the infection involving the central nervous system (5). Viremia occurs when the poliovirus is present in the blood stream, and this is usually seen in the asymptomatic cases. However, the ability for widespread cell tropism of the virus has allowed it to infect other tissues, some of which produce mild symptoms. Motor neurons themselves are attacked by the poliovirus, and these neurons also serve as a conduit for spreading, and this disease represents acute flaccid poliomyelitis(5). Acute flaccid paralysis is a common symptom, in which muscles do not respond well to contraction and thus slowly atrophy and become weakened. This is shown in loss of tendon reflexes, spasms, muscle weakness, followed by paralysis (6). Even after full recovery, post-polio syndrome can occur due to overall fatigue of remaining motor neurons to compensate for the function of lost motor neurons. The infection of the central nervous system is the main causative pathway for paralytic poliomyelitis. Different conditions of the disease are seen depending on where in the CNS the poliovirus infiltrates. This can be at any segment in the spinal cord, brain stem, or cortex. The motor functions are the most impaired in these cases, and this can manifest itself as weakness in the many skeletal muscles served by the CNS. The locations of the attack govern the designation of the poliomyelitis. Spinal polio is the most common, and is usually shown by paralysis of the legs, while bulbar polio can involve the brainstem and impair all the skeletal muscles that are served from the cranial nerves (6). It is also not uncommon to see a combination of these symptoms if the bulbar and spinal cords are affected, and this is called bulbospinal polio. The impact on the skeletal muscle of victims can involve the diaphragm, which aids in breathing. For those individuals, a external pressure apparatus is usually implemented throughout life.

Testing for the poliovirus can be done by analyzing the stool or the oral mucousa of the patient. This is effective since the mode of entrance for the poliovirus is orally. The cerebrospinal fluid can also be tested since in poliomyelitis, the poliovirus can cross the blood brain barrier (6). Unfortunately, treatments for poliomyelitis only involve stabilizing the symptoms. This utilizes pressure ventilators such as a chamber called an iron lung, which is now discontinued and replaced with more practical devices. If treatment is not given, in cases where respiratory weakness is present, death may occur due to unable for the individual to carry out inspiration. Poliomyelitis is not a curable disease since it is neurological in nature and neuronal growth once damaged is hard to produce. Neurons also usually do not replicate, which further curtails efforts to replace damaged motor neurons. However vaccines have been available to offer prevention of a full blown poliovirus infection. First it must be discussed that three different serotypes of the poliovirus exist (6). This indicates that combinations of these three strains are able to be implemented in the vaccine. A inactivated poliovirus vaccine uses formaldehyde to essentially make virus replication and infection impossible. This is the Salk vaccine, which is able to prevent paralytic polio in all cases (6). However a drawback of this vaccine is that it is not lifelong and thus be administered repeatedly throughout life. It is also administered through injection techniques (6). Another type preventive vaccine involves attenuated poliovirus called the Sabin vaccine, which can still induce a immune response and is able to replicate in the gastrointestinal mucousa, but the replication is inefficient. The administration of this vaccine is orally. Only a single dose of this vaccine is needed in life to ensure life-long immunity, however it may cause the individual to shed infectious virus and cause infection in others in rare cases (6). Both types of vaccines contain all three serotypes. Herd immunity also plays a crucial role in prevention. Since places like Mumbai are extremely populated, it is impractical for everyone to be vaccinated. Herd immunity prevents the poliovirus from spreading through a population. Other prevention techniques involve the improvement of water quality and sanitation conditions. Many rural and slums of India utilize a common public water source for bathing, and also for hydration. Due to the fecal-oral route of transfer of the poliovirus, many feces can leech out into the public water source and contribute to oral ingestion of the poliovirus. Therefore, providing clean water that is protected from human interaction, as well as proper waste disposal is imperative for the prevention of poliomyelitis.

Poliomyelitis has declined immensely in industrialized countries due to the implementation of vaccines in the 1950s (6). However the disease is still endemic in many third world countries where sanitary conditions are below average. However, global eradication initiatives have reduced the prevalence of poliovirus currently to only four countries, one of which is India. It is hard to eradicate the virus since unlike small pox, many asymptomatic carriers can exist. These individuals can act as reservoirs and transmit the virus through the population. Poliovirus infection also is more prevalent during the summer (6). Children are also the most likely to be affected due to the lack of opportunities to become vaccinated. In India, those that live in unsanitary conditions are most likely to be infected with the virus. Since the individuals are already born into poverty, good care for poliomyelitis is unavailable. Since manual labor is the most likely occupation for those suffering from poverty, the paralyzation of muscles and deformity eliminates this option. Victims must resort to begging for sustenance. However, recent efforts to spread awareness and show respect to polio victims, as well as provide education and support has improved the condition of many of those suffering from the debilitating effects, which are carried throughout life.

The Poliovirus is a positive stranded RNA virus that is transmitted fecal orally. The unique genome allows it to be a small capsid virus. Unique mechanisms to curtail host process as well as wide cell tropism allow it to be an efficient virus. The disease caused by the virus that is most detrimental is paralytic poliomyelitis. This is the rarest of conditions but it is very prevalent in some third world countries. Though global efforts to eradicate the virus through vaccination proved effective, it is now endemic in only a small number of nations. In the future, government implemented prevention programs as well as education will be the only means to effectively eradicate the effects of the poliovirus worldwide.

Works Cited Page

(1) John B. Carter and Venetia A. Saunders. Virology: Princles and Applications. Chichestire, England: John Wiley & Sons Ltd, 2007. Print.

(2) J. Lindsay Whitton, Christopher T. Cornell & Ralph Feuer. "Host and virus determinants of picornavirus pathogenesis and tropism." Nature Reviews Microbiology, 2005 3: 765-776.

(3) Mueller, Steffen, Eckard Wimmer, Jeronimo Cello, Eckard Wimmer, and Jeronimo Cello. "Poliovirus and Poliomyelitis: A Tale of Guts, Brains, and an Accidental Event." Virus Research, 2005 1111.2: 175-193.

(4) Tolskaya, EA, Romanova, LI, Kolesnikova, MS, Ivannikova, TA, Smirnova, EA, Raikhlin, NT, Agol, VI. Apoptosis-inducing and apoptosis-preventing functions of poliovirus J. Virol. 1995 69: 1181-1189.

(5) Arie J. Zuckerman, Jangu E. Banatvala, Barry D. Schoub, Paul D. Griffith, and Philip Mortimor. Principles and Practice of Clinical Virology. Chichestire, England: John Wiley & Sons Ltd, 2009. Print.

(6) Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Atkinson W, Wolfe S, Hamborsky J, McIntyre L, eds. 11th ed. Washington DC: Public Health Foundation, 2009.

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