About the Bluetongue Virus and West Nile Virus

In this step, we are going to learn about the bluetongue and West Nile fever viruses, about their structure and how they replicate. We will see that, despite being one of the RNA viruses and sharing their method of transmission through vectors, they are actually very different. Bluetongue virus) belongs to the genus Orbivirus in the family Reoviridae. This family includes more than 150 viruses that infect vertebrates, invertebrates, plants and fungi. It is a non-enveloped virus and with icosahedral symmetry, 80 nm in diameter.

It is composed of three concentric capsids: outer, middle, and inner. The outer capsid proteins (VP2 and VP5) are highly variable and determine the synthesis of neutralizing antibodies, resulting in up to 26 different viral serotypes, which do not induce cross immunity between them. This is a problem when designing vaccines. In addition, these external proteins are responsible for binding to the cell receptors. The inner capsid contains the genome, formed by double-stranded RNA distributed into 10 segments. 00:01:28.020 –> 00:01:33.700 Each of them is associated with a transcriptase and encodes a different protein.

The great genetic variety of this virus is due to point mutations in the genome or to the reassortment of the gene segments. This happens in other RNA viruses with several gene segments, as in the case of the influenza virus, which we will see next week. The replication begins by the recognition of the external proteins of the virus by the cell receptor. The virus enters the cell by endocytosis and loses the outer capsid. The inner capsid of the virus is preserved, since the double-stranded RNA is not natural for the cell and it must remain always protected. This is so that the cellular innate defence mechanisms are not activated.

Inside the internal capsid, the two strands of the RNA separate and they are transcribed to messenger RNAs that come out to the cytoplasm and are translated by the ribosomes. The proteins of the internal capsid and the transcriptases are synthesized first, and assemble as subviral particles. The new double-stranded RNA is transcribed inside these capsids. Later, the remaining proteins continue being transcribed and translated until the viral particles are complete. These new viral particles accumulate in the endoplasmic reticulum (RER) in the form of inclusion bodies. The mature viral particles are released when the plasma membrane of the cell is lysed. The West Nile virus (WNV) is a Flavivirus of the family Flaviviridae.

It is a spherical virus, of about 50 nm in diameter, with an envelope in which peplomers or spikes are inserted. These spikes consist of glycoprotein E and are highly immunogenic and induce neutralizing antibodies. The function of glycoproteins E is the binding to the cell receptor, allowing the entry of the virus into the cell.

Inside the viral particle there is the nucleocapsid, which encloses the genome: a molecule of positive- sense RNA (around 11 kb in size), which encodes a single polyprotein. The viral replication starts when the glycoproteins E bind to their cell receptor and the virus penetrates by endocytosis. Subsequently, the RNA is released into the cytoplasm. This is positive-sense RNA, which functions as messenger RNA. Ribosomes translate this viral RNA into a polyprotein that is cleaved into the structural and non-structural proteins. Thanks to the newly synthesized viral transcriptase, a negative-sense RNA complementary to the original genome is transcribed, which serves as a template for synthesizing new molecules of positive-sense RNA, identical to the original.

Assembly of the viral particles takes place in the endoplasmic reticulum, where they acquire the envelope as they bud into it.

Subsequently, viral particles are transported by the vesicles of the Golgi apparatus 00:04:26.960 –> 00:04:31.990 and the new viruses leave the cell through the secretory route.

Bluetongue virus and West Nile virus, despite being very different, they can replicate in the tissues of the insects that they infect, especially, in the salivary glands. This is so because these viruses are able to overcome the anatomical barriers and resist the innate immune response of insects, giving rise to persistent and systemic infections, but without causing damage. In this step, we have learned about the bluetongue virus and West Nile virus. In the next steps, we will see how they are capable of producing disease in the animals they infect.