Breaking it Down: Parts of a Virus

A virus is an acellular, parasitic entity, that is challenging to classify in the kingdom of living organisms because it is not considered to be alive. It has no plasma membrane, internal organelles, nor metabolic processes. It cannot divide nor reproduce by itself. Instead, it infects a susceptible host cell and hijacks the host’s cellular machinery to produce more viruses. Viruses can cause significant illness in humans and can be challenging to treat due to their diversity and ability to mutate. Understanding the structure of viruses and gaining an appreciation for this diversity can help one to understand the premise behind many current antiviral drug therapies and treatments.

The fully assembled infectious virus particle is called a virion. Virions are very small, about 20–250 nanometers (1 nanometer = 1/1,000,000 mm). Unlike bacteria (which are about 100 times larger), most viruses cannot be seen with a light microscope. To appreciate the size of a virus relative to other cells and organelles, see Figure 1.

The main function of the virion is to deliver its genome, or total genetic content, into the host cell so that the genome can be expressed (converted into proteins). Virus genomes tend to be small compared to bacteria or eukaryote (also known as an animal cell), as virus genomes tend to contain only those genes that code for proteins the virus cannot hijack from the host cell. The simplest viruses contain only enough RNA or DNA to encode four proteins, whereas the most complex viruses can encode 100 – 200 proteins. Thus, viruses rely heavily on their hosts to help them replicate and survive.

Classification of Viruses

Viruses are diverse and varied in their complexity. The simplest virions contain two basic components: a nucleic acid core (genetic material) and a capsid (an outer protective protein coat), jointly referred to as the nucleocapsid.

Unlike all living organisms that use DNA as their genetic material, viruses may use either DNA or RNA, which may be single stranded (ss) or double stranded (ds), linear or circular.

Some virus families have an additional outer covering surrounding the nucleocapsid, called an envelope. This is a lipid bilayer derived from the modified host cell membrane and studded with an outer layer of virus envelope glycoproteins. All viruses use some sort of glycoprotein to attach to their host cells via molecules on the host cell called viral receptors. The virus exploits these cell-surface molecules as a way to recognize and infect specific cell types. Attachment is a requirement for viruses to later penetrate the cell membrane, inject the viral genome, and complete their replication inside the cell.

DNA vs. RNA Viruses

DNA viruses have a DNA core. The viral DNA directs the host cell’s replication proteins to synthesize new copies of the viral genome, and to transcribe and translate that genome into viral proteins. DNA viruses cause human diseases such as chickenpox, Hepatitis B, and some venereal diseases like herpes and genital warts.

RNA viruses, comprising 70% of all viruses, contain only RNA in their core. To replicate their genomes in the host cell, the genomes of RNA viruses encode enzymes not found in host cells. Because of the error rate of the enzymes involved in RNA replication, these viruses show a much higher mutation rate than DNA viruses. For this reason, mutations (changes in the nucleotide sequence) occur more frequently in RNA viruses than in DNA viruses. This leads to more rapid evolution and variants in RNA viruses. For example, the fact that influenza is an RNA virus is one reason a new flu vaccine is needed every year. Human diseases caused by RNA viruses include Hepatitis C, measles, Ebola Virus Disease, rabies, and Covid-19.

A Covid-19 Focus

The coronavirus disease 2019 (Covid-19) pandemic is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is critical to find a specific treatment for COVID-19, and vaccines targeting various SARS-CoV-2 proteins are under development. Understanding the viral structure can help to uncover some of the challenges and opportunities to do so.

SARS-CoV-2 is an enveloped, single-stranded RNA virus. SARS-CoV-2 has four main structural proteins including the spike (S) glycoprotein, small envelope (E) glycoprotein, membrane (M) glycoprotein, and nucleocapsid (N) protein, and also several accessory proteins (Figure 3). The bulbous projections seen on the outside of the coronavirus are spike (S) glycoproteins, which gives the virus its crown-like appearance under a microscope (“corona” is “crown” in Latin). The S protein is the main antigen component in all structural proteins of SARS-CoV-2. This protein binds to the host cell and acts as a hook to allow the virus to latch onto host cells and open it up for infection. It is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor, angiotensin-converting enzyme 2 (ACE2), expressed on many human cells (one of the most frequently expressed locations includes lower respiratory tract cells), while the S2 subunit mediates viral cell membrane fusion. Considering the S protein is critical for the entry of the coronaviruses, it is an attractive antiviral target.

Summary

Viruses are diverse. They vary in their structure, replication methods, and in their target hosts, which range from bacteria and archaea to plants and animals. Viruses cause a variety of diseases in humans and animals. Some of these diseases can be prevented by the use of viral vaccines, which stimulate protective immunity against the virus without causing major disease. In addition, antiviral drugs and therapies are often employed to target enzymes and other viral proteins, in particular when no effective vaccine is available or the viruses are subject to mutations. Considering the diversity of viruses, hopefully you may now appreciate where the landscape of therapeutics is heading.

References:

Astuti, I., & Ysrafil (2020). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes & metabolic syndrome, 14(4), 407–412. https://doi.org/10.1016/j.dsx.2020.04.020

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Huang, Y., Yang, C., Xu, X. et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 41, 1141–1149 (2020). https://doi.org/10.1038/s41401-020-0485-4

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