Influenza Virus Replication Cycle

Transcription is the formation of an RNA strand from a DNA template within the nucleus of a cell. There are four nucleotides of DNA. These are adenine, cytosine, guanine and thymine. These nucleotides are transcribed to form messenger ribonucleic acid (mRNA) consisting of nucleotides made of adenine, cytosine, guanine and uracil. This transcription from DNA to mRNA happens by an RNA polymerase II. This newly created mRNA is read in the 5' to 3' direction in sets of 3. These sets are called codons. Each mRNA also has a cap and end. On the 5 prime side is a methylated guanine triphosphate and on the 3 prime is a poly A tail. Messenger RNA then moves to the cells cytoplasm and through the cells ribosomes for translation. Messenger RNA is matched to molecules of transfer RNA (tRNA) in the ribosomes to create amino acids. These amino acids subsequently form an amino acid chain. (Osuri, 2003) A visual representation of this can been viewed in figure 3.

Through reverse transcriptase, the DNA is made and put into the genome of the host cells. The cell then uses 9 genes and produces all the protein and RNA needed to make more virus particles, thus reproducing.

First of all, the name “Influenza” is derived from the Latin word for “influence”, and it is an infectious disease that is caused by the RNA viruses from the Orthomyxoviridae family:

The virus fuses with the cell’s plasma membrane. The capsid proteins are removed, releasing the viral proteins and RNA. Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. Reverse transcriptase catalyzes the synthesis of a second DNA strand complementary to the first. The double-stranded DNA is incorporated as a provirus into the cell’s DNA. Proviral genes are transcribed into RNA molecules, which serve as genomes for the next viral generation and as mRNAs for translation into viral proteins. The viral proteins include capsid proteins and reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER). Vesicles transport the glycoproteins from the ER to the cell’s plasma membrane. Capsids are assembled around viral genomes and reverse transcriptase molecules. New viruses bud off from the host cell.

Influenza viruses need to infect host cells in order to replicate. Most flu viruses are destroyed by the innate immune mechanisms involving components such as macrophages, interferons and natural killer cells, however some manage to avoid being detected by these early defence mechanisms and so are eliminated by the adaptive immune response.

As soon as the virus is in the body, it uses the hemagglutinin to bind to the cell surface. The membranes of the virus and the cell fuse togather and the capsid that contains the single stranded RNA is released into the cytoplasm. The protein coat of the virus dissassembles and then starts making viral proteins and viral RNA copies. The new virus proteins are put togather near the cell membrane and then bud off from the membrance. Influenza has a rapid onset and pronounced symptoms. After the influenza virus invades a person’s body, an incubation period of one to two days passes before symptoms appear. For most people flu symptoms begin to subside after two to three days and disappear in seven to ten days. However, symptoms like coughing and fatigue may persist for two

There are there types of influenza A and C or the most severe types and B which is the most common, Luckily not the to severe. The virus works by first attaching to the outside of a host cell. It injects its RNA into the cell. Unfortunately our cells treat the RNA like they should. It translates the viral genes using the cell’s ribosomes and enzymes. Now the virus can take the cell over and use it to reproduce more viruses. Sooner or later it releases the new nauseating viruses and they search for another cell to raid.

There are two important proteins used in the determination of the type of influenza; haemagglutinin (HA) and neuraminidase (NA). There are 18 known variations of the haemagglutinin protein and 11 of the neuraminidase protein, giving hundreds of possible variations in the subtypes of the virus . These subtypes are further divided into different strains that have a divergent molecular makeup, giving rise to viruses that differ in virulence, ease of transmission and severity of symptoms. Not all strains of influenza can cause disease in humans; influenza D subtypes cannot infect humans and influenza C infections are rare and usually very minor. Influenza A and B are the subtypes that are responsible for the common infections and the epidemics and pandemics that occur periodically, with influenza A causing the majority of these infections. The virus is transmitted through the inhalation of droplets which are expelled when an infected person coughs or sneezes, through contact with a contaminated surface and through the exchange of saliva . The infected person becomes infectious to others around 12 hours after first contact with the virus and remains contagious for around the next five days; this can vary as the immunocompromised can take longer to subdue the virus and children tend to be more infectious than adults . The virus incubates in the respiratory tract by invading cells through the cleavage of the viral protein haemagglutinin by human proteases . The pathogenicity of a certain strain is determined by the spread of proteases in the respiratory tract that can cleave the proteins of the virus; a strain is typically milder if the proteases that reside in the lungs and throat are the only ones capable of cleaving the virus, causing an upper respiratory tract (URT)

The influenza virus thrives because of its unique characteristics that allow it frequently change and undergo evolution. The influenza virus has a segmented genome meaning that each section of RNA is copied separately allowing reassortment to play a major role in the evolution of the influenza virus. When two different strands of the virus attack the same cell, both strands of RNA are copied in the nucleus. These copies then move to the cytoplasm where new viruses are compiled. Each new virus needs all eight of its genomes which can come from a copy of either of the original infecting viruses. The new virus would then have a mixture of RNA from each originating virus causing it to be different from both (Rahnama, L, et al., 2013). Reassortment causes new strains of viruses

(Silverstein: 13) There are three types of influenza, depending on their activity: type A, which is usually the cause of outbreaks; type B, which is linked to sporadic cases, and type C, which rarely causes disease reactions. (Silverstein: 54) The virus which causes influenza enters the host through the respiratory tract, and binds itself to epithelial cells. The virus causes the cell to engulf it by endocytosis, and then fuses to the wall of the endocytic vesicle, injecting the contents of the virus into the cytosol of the cell. The RNA of the virus enter the nucleus of the cell, and spur the creation of new copies of the genes. These genes, as well as new viral proteins that are created in the cell, leave the cell as fresh viruses, budding off the plasma membrane of the cell.

Influenza is an acute condition that results in high fever, a dry cough and sore throat, body aches, headache, runny nose and malaise upon contracting the influenza virus (1). These symptoms often progress into more severe conditions and in certain populations; infection with influenza can lead to death. The influenza virus is an RNA virus that belongs to the family orthomyxoviridae. There are three types of influenza virus and they are classified as type A, type B and type C (2).

Once tightly bound the virus is endocytosed via coated vesicles. The virus is transported into late endosomes which acidify their content and hence induce conformational rearrangement of HA exposing the fusiogenic peptide sequence. The loop region of the HA becomes a coiled coil that mediates membrane fusion. The release of viral genome into the cytoplasm also requires protons that are pumped from the acidic endosome into the virion interior via the matrix protein M2 that acts as a proton channel. Viral RNA dissociates from M1 and is then imported in an ATP-dependent manner into the nucleus for transcription and translation. In humans, the replication of the influenza virus is usually restricted to the airways epithelial cells due to the limited expression of a serine protease, produced by nonciliated bronchial epithelial cells and which cleaves the HA precursor in HA1 and HA2 polypeptides, rendering the virions infectious. Replication and virions production occurs within hours after virus entry. The viral ribonucleoprotein (vRNP) complexes are released from the endosomes into the cytoplasm and subsequently transported to the nucleus, where replication and transcription take

Influenza is one of the most important human respiratory infections and its seasonal recurrence is a major contributor to human morbidity and mortality. Seasonal influenza has an estimated annual attack rate of 10-20%, leading to 3-5 million cases of severe illness and 250,000 to 500,000 deaths each year [1]. Throughout history, influenza A has also been the greatest contributor of human pandemics. During the last century, four influenza A pandemics (1918, 1957, 1968 and 2009) caused over 50 million deaths globally, created significant social and economic impact on the human society, and shaped future research and public health policies.

Influenza also known as the “Flu” is an ongoing health concern each year. It is most prevalent during the fall and winter seasons. Influenza is highly contagious and can spread rapidly when precautions are ignored. Every year numerous cases erupt despite education, health promotion and vaccinations. Flu related complications result in hospitalizations and even death each year, costing billions of dollars to be used in treatment and income lost due to sick days and unproductivity on the infected person’s behalf. Zimmerman et al. 2010 concurs stating, “Seasonal influenza leads to about 36,000 deaths annually in the United States and more than 226,000 hospitalizations.” (Zimmerman et al. 2010). Loerbroks et al. 2012 also states “Influenza and

The influenza virus usually has a round shape; it can be elongated or even have an irregular shape at times. In addition, it has a layer of spikes on its exterior. Note that there are two different types of these spikes. Each spike has its own protein, one is the hemagglutinin (HA) protein and the other is the neuraminidase (NA) protein. The HA protein lets the virus to attach to a cell, so it can enter into a host cell and start the infection process (every virus must enter cells in order to make more copies of themselves). The NA protein is needed for the virus to leave the host cell, so that new viruses that were made inside the host cell can infect more cells. Because these proteins are present on the surface of the virus, they are visible to the human immune system. Inside the layer of spikes, are eight pieces of RNA that contain the genetic information for making new copies of the virus. Each segment contains instructions to make one or more proteins of the virus.