Virus Structure

A virus is a parasitic particle that is not able to replicate its own mechanisms due to a lack of many organelles, so it infects cellular machinery to direct synthesis of proteins important for viral replication. The virus will direct cellular machinery to synthesize mRNA, virus-specific proteins which will utilize the host cell’s tRNA, and translation factors.

Structure

The nucleic acid of a virus is enclosed by the protein capsid, which is made from a small number of proteins (as viruses have a limited number of genes in the form of DNA or RNA) each encoded by the viral genome. The capsid which encloses the viral genome together is the nucleocapsid, and the capsid is made from protein subunits (capsomeres). The genetic material of viruses can be single or double stranded, linear or circular, and some viruses will have several nucleic acid structures in the form of segments.

The first type of viral structure is a helical structure, which is formed from single capsomere subunits stacked together to form a tube with the RNA, bound to the helix structure through negatively charged phosphates of nucleic acids and positively charged proteins. The longer the helix, the more genetic material is contained. An example of a virus with a helical structure for capsid protein arrangement is the tobacco mosaic virus (TMV).

The other major viral structure is icosahedral, which has a minimum of 20 faces made from equilateral triangles. Each face is made from three identical capsomeres, hence a minimum of 60 protein subunits are used for the formation of the capsid. The majority of viruses with this structure (eg. tobacco satellite necrosis virus, poliovirus, rhinovirus, adenovirus) are specific to animals.

Some viruses will also have an envelope made from the phospholipid membranes (either internal or external) of the host cells and viral glycoproteins. The viral envelope allows for the virus to remain undetected by the immune system, and to fuse with the host cell plasma membrane through receptor mediated endocytosis using the glycoproteins. When the replicated viral particles leave the host cell, the host cell is weakened, but the viral particle can only survive outside of a host cell for a limited time, as the viral envelope is sensitive to desiccation, heat and detergents.

RNA viruses

RNA viruses encode for the synthesis of enzymes (eg. RNA polymerases, RdRp, helicase, capping enzymes, NTPase, and non enzymatic proteins used in viral replication) which are able to replicate RNA into DNA, as this cannot be done by the host cell. These enzymes are more likely to make errors than DNA polymerase so RNA viruses mutate more often, which allows for faster adaptation to changes in the external environment.

Single stranded RNA viruses

Positive strand RNA viruses have a positive sense, single stranded genome, made from RNA, where the polarity of the genomes allows for the positive sense to be used as mRNA and to be directly translated into viral proteins by the host’s ribosomes. The RNA dependent RNA polymerase enzyme (RdRp) is used in replication of the genome to synthesize negative sense antigenomes which are used as templates to create positive sense genomes.

The first proteins to be expressed after infection are viral replication complexes which allow for association with intracellular membranes. Then replication of the genome occurs through double stranded intermediates in the organelles to avoid cellular responses to the infection.

The negative strand RNA viruses are complementary to the mRNA so it has to be converted into a positive sense RNA by RNA polymerase prior to genome replication.

HIV infection

The HIV virus infects helper T cells (CD4+), macrophages, and dendritic cells. This leads to lower levels of CD4+ cells due to pyroptosis (cell death of infected cells), apoptosis (cell death) of uninfected cells, direct viral killing of infected cells, and killing of infected CD4+ cells by CD8+ cytotoxic lymphocytes. When the level of CD4+ cells decreases, cell mediated immunity is lost which leads to the development of a syndrome (a condition with a set of different symptoms existing at the same time, with the severity differing between individuals).

The virus replicates within the host cell with the use of reverse transcriptase, which forms a complementary DNA molecule. This process can result in many errors, hence the mutations could lead to drug resistance or prevent the virus from being detected by the immune system.

The virus is surrounded by proteins (gp120), and the capsid contains the viral RNA and viral enzymes. The gp120 protein will bind to the CD4 receptor on a macrophage and a second receptor (CCR5) will allow for the virus to enter the cell through endocytosis. This releases viral RNA and viral enzymes. Reverse transcriptase is used to synthesize a strand of viral DNA and then a complementary DNA strand. The viral DNA then moves to the nucleus of the cell so that it is integrated into the DNA of the host cell by the integrase enzyme. The transcription of the DNA will then lead to the production of viral DNA, and the synthesis of viral proteins. The gene coding for gp120 production is altered by a mutation, which leads to co-receptor allegiance. The virus will then bind to CXCR4 receptors which are present on CD4+ T helper cells. The process of replication occurs again, but when the virus leaves the cell the membrane is ruptured which kills the T helper cell and decreases their levels in the body.

Influenza infection:

Influenza infections occur in columnar epithelial cells in the respiratory tract, where viral hemagglutinin binds to sialic acid receptors on the epithelial cells, leading to endocytosis of the viral particle. For this event to occur, the influenza virus must mutate at the receptor binding sites of hemagglutinin to cross the interspecies barrier from birds to humans. At the same time, there must be mutations in neuraminidase, an enzyme used to cleave the sialic acid molecule and free the virus to infect other cells in the host, so that virus retains its virulence.

When the viral particle has entered the host cell endosome, the acidic conditions cause the hemagglutinin protein to fuse with the viral envelope which leads to ion channels allowing proton movement into the viral envelope. The acidic conditions cause the core of the virus to disassemble and release the viral RNA with the core proteins.

The core proteins and viral RNA form a complex which is transported into the nucleus where the RdRp transcribes the complementary positive sense viral RNA (influenza is negative sense so it must be converted into positive sense) and is then translated in the cytoplasm. Some of the proteins are moved back into the nucleus to degrade cellular mRNA and prevent translation of the cellular mRNA, and some of the viral proteins are secreted by the Golgi apparatus onto the cell surface.

The negative sense viral RNA and viral proteins are assembled to for a virion, where the viral core proteins leave the nucleus and enter the protrusion on the cell membrane so the mature virions (protein capsules on the virus particles) are able to bud from the cell with the phospholipid membrane and detach with the use of neuraminidase to cleave the sialic acid from the host cell.

References

• Positive-Strand RNA Viruses in Animals | Boundless Microbiology (2020). Available at: https://courses.lumenlearning.com/boundless-microbiology/chapter/positive-strand-rna-viruses-in-animals/ (Accessed: 17 August 2020).

• RNA virus (2020). Available at: https://en.wikipedia.org/wiki/RNA_virus (Accessed: 17 August 2020).

• Structure of Viruses | Boundless Microbiology (2020). Available at: https://courses.lumenlearning.com/boundless-microbiology/chapter/structure-of-viruses/ (Accessed: 17 August 2020).

• 9.10A: Double-Stranded RNA Viruses - Retroviruses (2017). Available at: https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/9%3A_Viruses/9._10%3A_Retroviruses%3A_Double-Stranded_RNA_Viruses/9.10A%3A_Double-Stranded_RNA_Viruses_-_Retroviruses (Accessed: 17 August 2020).

• Bernd Sebastian Kamps, a. (2020) Influenza Book | Pathogenesis and Immunology , Influenzareport.com. Available at: http://www.influenzareport.com/ir/pathogen.htm (Accessed: 17 August 2020).