The World Health Organization (WHO) considers dengue to be the most prevalent vector-borne viral disease affecting humans worldwide. The illness is one of the most common, mostly in the tropical and subtropical regions of the world. According to the statistics by Chen et al., (2018), about half of the world population lives in areas that are disease prone. According to Khetarpal & Khanna (2016), the condition affects about 390 million people each year. Dengue fever is a self-limiting acute disease typified by severe flu-like symptoms. The disease has numerous range of symptoms such as fever, joint, and muscle pain. In other severe cases, the disease leads to severe headache, retro-orbital pain, and, in other instances, rashes. The microbiology of Dengue fever looks to pinpoints the pathology of the disease. It seems to assess some of the four viruses that are the causative factors of the disease. In this article, therefore, the aim is to discuss Dengue regarding its microbiological aspects.
The Diseases Background
According to Chen et al., (2018) , “Dengue infections caused by the four antigenically distinct dengue virus serotypes (DENV1, DENV2, DENV3, and DENV4) of the family Flaviviridae” (614).The disease is one of the most important arboviral diseases in humans, in terms of geographical distribution, morbidity, and mortality ( Chen et al., (2018). Dengue is one of the conditions whose burden is high in the world. According to the statistic from the year 2018, the burden of the disease is about 500,000, with its risk of infection hitting 2.5 billion globally. According to the epidemiology on the condition, Dengue affects every country with more than 500 000 cases of severe dengue and 20 000 deaths reported annually on over 100 countries in the world ( Khetarpal & Khanna, 2016). The statistics show that the disease is dangerous, and the steps to curb its spread and mitigate its effect should be the priority to every country in the world.
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A person infected by the disease exhibits numerous range of symptoms. The symptoms vary depending on the severity of the disease. Notably, the virus comes in different forms, and each type has a specific symptom that can be life-threatening. Dengue can either be Dengue Fever (DF) to a fatal syndrome called Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS) ( Khetarpal & Khanna, 2016). For the disease, a sudden high fever or a sudden headache are some of the unique traits. Alsop, the disease leads to high or sharp pain behind the eye, while in most cases, severe joint pain and body ache are present. Also, patients are likely to experience fatigue and skin rash. Other most fatal symptoms include severe headache and nose bleeding.
Understandably, most people mistake Dengue with flu because of the similarities in symptoms between the two diseases. However, a blood test to check for the virus or antibodies is always the approach that most physicians take to diagnose the condition. The patient should alert the doctor if they have a history of travel, mostly in the areas that are prone to disease, as this can help with the diagnosis. Though vaccine does exist, Dengue is a viral disease, and like any other viral disease, there is no specific treatment approach for the disease. Therefore, the treatment approach used for the disease is to eliminate the symptoms. Implying that, if a person has a fever, they should manage the fever by taking drugs such as acetaminophen , but avoid medications that can induce severe bleeding such as the aspirin. The prevention measure is strategies to reduce being in contact with the mosquito that spread the virus.
Microbiology of the Dengue
The Dengue Serotypes
The Dengue virus (DENV), a mosquito-borne flavivirus, is the leading cause of the Dengue disease. According to Khetarpal & Khanna (2016), “DENV is a single-stranded RNA positive-strand virus of the family Flaviviridae, genus Flavivirus”(34). The Dengue genus comes in different forms and shapes. The genus may include the West Nile virus and the common yellow fever virus. The Tick-borne Encephalitis Virus, several other viruses that may cause encephalitis, are other forms of Dengue genus. In the human system, Dengue can cause a wide range of life-threatening diseases. These may include the self-limited Dengue Fever (DF) and the Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS) , whichis a life-threatening syndrome.
There are four known serotypes of the Dengue disease despite the report that there is a firth discovery of the Dengue serotype. The four known include theDENV-1, DENV-2, DENV-3, and the DENV-4. The division of the four stereotypes considers the virus classification based on the antigen found on the surface of the virus. "These four subtypes are different strains of dengue virus that have 60-80% homology between each other” (Chang et al., 2017). The difference between the Dengue viruses in humans is the distinction on the surface proteins of the different dengue subtypes. According to Khetarpal & Khanna (2016), “Infection induces long-life protection against the infecting serotype, but it gives only a short time cross-protective immunity against the other types” (123). The first infection, which in this case is the DENV-1, is linked to a minor disease for a human being. However, the later phases of the disease, such as DENV-2, DENV-3, and DENV-4, cause severe infections in both children and adults.
Dengue Virus Microscopic Features
Dengue virus under the microscope reveals thatDENV is about 50-nm virus. The microscope view shows that the virus is enveloped with a lipid membrane for both protection and attachment with other bodies. Also, microscopic observation reveals that the Dengue virus has about 180 identical copies of the envelope (E) protein. The proteins are attached to the outer surface of the viral membrane by a short transmembrane segment. Dengue virus has a genome “of about 11000 bases that encodes a single large polyprotein. The polyprotein is subsequently cleaved into several structural and nonstructural mature peptides” ( Chakravarti et al., 2016). These are a critical feature that differentiates the virus and make it lethal for the human being. These are also the features that enable the virus to survive for long in a specific host environment. Dengue polyprotein has about structural proteins. They include C, prM, and E. The polyprotein also has about seven nonstructural proteins. These seven groups include the NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5 ( Banerjee, Paul & Bandyopadhyay, 2018). Lastly, the polyprotein also has both 5' and 3' end as a short non-coding region for the virus.
Microscopic observation reveals that structure such as the envelope (E) glycoprotein capsid, (C) protein, and the membrane (M) protein are the dengue structure proteins. The observation reveals that the dengue protein structure derived by furine-mediated cleavage from a prM precursor. According to Chen et al. (2018), “the E glycoprotein is responsible for virion attachment to receptor and fusion of the virus envelope with the target cell membrane and bears the virus neutralization epitopes” (640).Only one other viral protein, NS1, other than the E glycoprotein, has been associated with a role in protective immunity. The NS3 is a protease and a helicase, whereas NS5 is the RNA polymerase in charge of viral RNA replication.
Dengue Virus Life Cycle
The life cycle of the disease is a complex process that involves a lot of factors that, in the end, lead to its survival and growth to a point where it causes havoc to the human system. Seven steps take place during the life cycle of the virus. For the flavivirus life cycle, the first step is the binding process of the virus. At this stage, the virus can bind to cell-surface attachment molecules and receptors. After the binding, the process called endocytosis allows the virus to be internalized (Chang et al., 2017). The next step after the internalization takes place because of the low pH of the endosome. At this phase, the cellular membrane and the virus fuse through the mediation of the viral glycoproteins. The viral fusion with the cell membrane allows the virion to disassemble. The dissembling virion thus permits the release of the vRNA into the cytoplasm, which is critical during the life cycle of the disease.
The third step involves the translation of the product of the second step, which is the vRNA into a polyprotein. The polyprotein is processed through the aid of the cellular proteases and the virus ( Chakravarti et al., 2016). Next is the replication of the genome RNA by the viral NS proteins. The replication allows the virus to assemble at the endoplasmic reticulum (ER) membrane. Notably, the ER is the site that houses the C protein and vRNA and enables them to develop. At the ER also, the C protein and vRNA combines with the membrane and glycoproteins to form immature virus particles. Through the use of the secretory pathway, the product or the immature virus particles are permitted to move from ER to the acidic environment of the trans-Golgi network (TGN). At the TGN, the furin-mediated cleavage of prM drives plays a critical role in driving the maturation of the immature virus particles to the mature virus. The mature virus gets released into the cell, and this causes the disease to a human being. Therefore, this complex process is the entire chain the virus follows until it is released into the cell where it causes disease.
Dengue Virus Entry intothe Cell
The Dengue virus follows a complicated path towards entering the cell and causing dengue disease. The receptor-mediated endocytosis plays a critical role in mediating viral entry into the cells. For the viral dengue to enter the cell, there must be a presence of the Candidate cellular receptors. These receptors can either be dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), various glycoproteins, or a mannose receptor ( Chakravarti et al., 2016). Also, the human C-type lectin-like molecule CLEC5A plays a critical role in the virus entry into the cell. The molecule plays an essential part as a macrophage receptor for DENV. In doing so, the human C-type lectin-like molecule CLEC5A, is a proinflammatory receptor for DENV.
According to Banerjee, Paul & Bandyopadhyay (2018), “there is a consensus that the viral E glycoprotein affects host cell receptor binding, viral entry, and is a major target for humoral immunity” (395).Three domains exist to form the composition of the E protein. The domain includes the domain I, domain II and domain III. The domain II has a distal tail whose role is to harbor the fusion peptide.On the other hand, domain III is responsible for the receptor-binding activity. According toChakravarti et al., (2016), the “Low-pH–induced trimerization exposes the hydrophobic fusion peptide in a manner consistent with membrane fusion mediated by class II fusion protein” (83). Note that the glycosylation pattern differs. The differences come due to the differences in the DENV serotype. The differences in the DENV strains also create a difference in the glycosylation pattern. The cause of this difference also comes due to the difference in the cells in which the virus is propagated.
After the internalization, as described above, the virus undergoes the process of intrinsic uncoating via different internal processes. The protein envelopes lays flat on the surface of the virus when carried on its infectious form into the cell. After laying on the virus surface, the envelope protein forms a smooth coat with icosahedral symmetry. However, the entry is different when the virus enters the cell and into lysosomes in its non-infectious status or form. In such a case, the environment where the virus enters is acidic. The acidic environment is critical in allowing or triggering the snapping of the protein into many shapes. The snapping proteins thus assemble at the site called the trimeric spike. There are several hydrophobic amino acids at the trimeric spike at the tip ( Chakravarti et al., 2016). The hydrophobic amino acids thus help insert the proteins into the lysosome membrane. Therefore, it causes the virus membrane to fuse with lysosomes. The fusion between the virus membrane and the lysozyme is the trigger of the infection. The fusion releases the RNA into the cell, and this marks the beginning of the diseases. Therefore, through this complicated process, the virus finds its way into the cell. Through the help of different chemical processes within the cell, the virus interacts with numerous processes and chemicals to initiate the infection process.
In conclusion, the dengue virus has complex microbiology, which consists of its structure, the serotypes, and the modes of entry into the cell, where it leads to infections. The article has covered some of the essential and complex microbiology of the disease. These include its four serotypes, which are the most known in the field of Microbiology. The discussion has also covered the mode of entry into the body, the life cycle, and the microscopic structures.
References
Banerjee, A., Paul, U. K., & Bandyopadhyay, A. (2018). Diagnosis of dengue fever: roles of different laboratory test methods. International Journal of Advances in Medicine , 5 (2), 395-9.
Chakravarti, A., Roy, P., Malik, S., Siddiqui, O., & Thakur, P. (2016). A study on gender-related differences in laboratory characteristics of dengue fever. Indian journal of medical microbiology , 34 (1), 82.
Chang, K., Lee, N. Y., Ko, W. C., Tsai, J. J., Lin, W. R., Chen, T. C., ... & Chen, Y. H. (2017). Identification of factors for physicians to facilitate early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever in Taiwan. Journal of Microbiology, Immunology and Infection , 50 (1), 104-111.
Chen, C. H., Huang, Y. C., Kuo, K. C., & Li, C. C. (2018). Clinical features and dynamic ordinary laboratory tests differentiating dengue fever from other febrile illnesses in children. Journal of microbiology, immunology, and infection , 51 (5), 614-620.
Khetarpal, N., & Khanna, I. (2016). Dengue fever: causes, complications, and vaccine strategies. Journal of immunology research , 2016 .
