Viruses

Dr. Becki Brunelli

Viruses

Learning Objectives

By the end of this section, you will be able to:

Describe how viruses were first discovered and how they are detected
Explain the detailed steps of viral replication
Describe how vaccines are used in prevention and treatment of viral diseases

In A, an electron micrograph shows the tobacco mosaic virus, which is shaped like a long, thin rectangle. Photo B shows an orchid leaf in varying states of decay. Initial symptoms are yellow and brown spots. Eventually, the entire leaf turns yellow with brown blotches, then completely brown.

Figure 11.2 (a) The tobacco mosaic virus, seen by transmission electron microscopy, was the first virus to be discovered. (b) The leaves of an infected plant are shown. (credit a: scale-bar data from Matt Russell; credit b: modification of work by USDA, Department of Plant Pathology Archive, North Carolina State University)

No one knows exactly when viruses emerged or from where they came, since viruses do not leave historical footprints such as fossils. Modern viruses are thought to be a mosaic of bits and pieces of nucleic acids picked up from various sources along their respective evolutionary paths. Viruses are acellular, parasitic entities that are not classified within any domain because they are not considered alive. They have no plasma membrane, internal organelles, or metabolic processes, and they do not divide. Instead, they infect a host cell and use the host’s replication processes to produce progeny virus particles. Viruses infect all forms of organisms including bacteria, archaea, fungi, plants, and animals. Living things grow, metabolize, and reproduce. Viruses replicate, but to do so, they are entirely dependent on their host cells. They do not metabolize or grow, but are assembled in their mature form.

Viruses are diverse. They vary in their structure, their replication methods, and in their target hosts or even host cells. While most biological diversity can be understood through evolutionary history, such as how species have adapted to conditions and environments, much about virus origins and evolution remains unknown.

How Viruses Replicate

Virions, single virus particles, are very small, about 20–250 nanometers (1 nanometer = 1/1,000,000 mm). These individual virus particles are the infectious form of a virus outside the host cell. Unlike bacteria (which are about 100 times larger), we cannot see viruses with a light microscope, with the exception of some large virions of the poxvirus family (Figure 11.3).

Relative sizes on a logarithmic scale, from 0.1 nm to 1 m, are shown. Objects are shown from smallest to largest. The smallest object shown, an atom, is about .1 nm in size. A C60 molecule, or buckyball, is 1 nm. The next largest objects shown are lipids and proteins; these molecules are between 1 and 10 nm. The influenza virus is about 100 nm. Bacteria and mitochondria are about 1 µm. Human red blood cells are about 7 µm. Plant and animal cells are both between 10 and 100 µm. Pollen from a morning glory flower and a human egg are between 100 µm and 1 mm. A frog egg is about 1 mm.

Figure 11.3 The size of a virus is very small relative to the size of cells and organelles.

The use of technology has allowed for the discovery of many viruses of all types of living organisms. They were initially grouped by shared morphology, meaning their size, shape, and distinguishing structures. Later, groups of viruses were classified by the type of nucleic acid they contained, DNA or RNA, and whether their nucleic acid was single- or double-stranded. More recently, molecular analysis of viral replication cycles has further refined their classification.

The most visible difference between members of viral families is their morphology, which is quite diverse. An interesting feature of viral complexity is that the complexity of the host does not correlate to the complexity of the virion. Some of the most complex virion structures are observed in bacteriophages, viruses that infect the simplest living organisms, bacteria.

An illustration shows bacteriophage T4, which houses its DNA genome in a hexagonal head. A long, straight tail extends from the bottom of the head. Tail fibers attached to the base of the tail are bent, like spider legs. An adenovirus houses its DNA genome in a round capsid made from many small capsomere subunits. Glycoproteins extend from the capsomere, like pins from a pincushion. The HIV retrovirus houses its RNA genome and an enzyme called reverse transcriptase in a bullet-shaped capsid. A spherical viral envelope, lined with matrix proteins, surrounds the capsid. Glycoproteins extend from the viral envelope.

Figure 11.5 Viruses can be complex in shape or relatively simple. This figure shows three relatively complex virions: the bacteriophage T4, with its DNA-containing head group and tail fibers that attach to host cells; adenovirus, which uses spikes from its capsid to bind to the host cells; and HIV, which uses glycoproteins embedded in its envelope to do so. Notice that HIV has proteins called matrix proteins, internal to the envelope, which help stabilize virion shape. HIV is a retrovirus, which means it reverse transcribes its RNA genome into DNA, which is then spliced into the host’s DNA. (credit “bacteriophage, adenovirus”: modification of work by NCBI, NIH; credit “HIV retrovirus”: modification of work by NIAID, NIH)

Viruses are distinct from all other life forms in that their genetic material can be either DNA or RNA, with their genomes being relatively small and streamlined to include only the genes necessary for producing proteins not available from the host cell. These genomes vary in structure, being single or double-stranded, and can be either linear or circular, sometimes consisting of multiple segments. DNA viruses, which include chickenpox and hepatitis B and some sexually transmitted infections like herpes and HPV, replicate by commandeering the host cell’s replication machinery to produce viral DNA and proteins. On the other hand, RNA viruses, responsible for illnesses like influenza, hepatitis C, measles, and rabies, must synthesize their own replication enzymes, leading to a higher mutation rate during genome replication. This high mutation frequency contributes to their rapid evolution and the need for annual updates in vaccines, such as those for the flu.

Steps of Virus Infections

A virus must “take over” a cell to replicate. The viral replication cycle can produce dramatic biochemical and structural changes in the host cell, which may cause cell damage. These changes, called cytopathic effects, can change cell functions or even destroy the cell. Some infected cells, such as those infected by the common cold virus (rhinovirus), die through lysis (bursting) or apoptosis (programmed cell death or “cell suicide”), releasing all the progeny virions at once. The symptoms of viral diseases result from the immune response to the virus, which attempts to control and eliminate the virus from the body, and from cell damage caused by the virus. Many animal viruses, such as HIV (human immunodeficiency virus), leave the infected cells of the immune system by a process known as budding, where virions leave the cell individually. During the budding process, the cell does not undergo lysis and is not immediately killed. However, the damage to the cells that HIV infects may make it impossible for the cells to function as mediators of immunity, even though the cells remain alive for a period of time. Most productive viral infections follow similar steps in the virus replication cycle: attachment, entry, replication, assembly, and release.

Viruses replicate by starting with the attachment to a host cell. They have specific proteins that precisely fit receptor sites on the cell’s surface, ensuring that they only attach to compatible host cells. Once attached, different viruses have different methods of entry: bacteriophages, which infect bacteria, inject their genetic material, leaving their shell outside, while other viruses are engulfed by the host cell or fuse with its membrane to enter. Inside the cell, the virus’s genetic material is freed to begin the replication process.

The replication depends on the type of virus. DNA viruses typically use the host’s cellular machinery to duplicate their DNA and produce their proteins. RNA viruses often need to bring in their own enzymes because the host cell usually doesn’t have the necessary tools for replicating RNA. Following replication, the newly created viral components are assembled into complete viruses. Following assembly, new viruses are released from the host cell, either by causing the cell to break open or by budding off in a way that doesn’t immediately destroy the cell, ready to infect new cells and continue their life cycle.

The illustration shows the steps of an influenza virus infection. In step 1, influenza virus becomes attached to a receptor on a target epithelial cell. In step 2, the cell engulfs the virus by endocytosis, and the virus becomes encased in the cell’s plasma membrane. In step 3, the membrane dissolves, and the viral contents are released into the cytoplasm. Viral mRNA enters the nucleus, where it is replicated by viral RNA polymerase. In step 4, viral mRNA exits to the cytoplasm, where it is used to make viral proteins. In step 5, new viral particles are released into the extracellular fluid. The cell, which is not killed in the process, continues to make new virus.

Figure 11.6 In influenza virus infection, glycoproteins attach to a host epithelial cell. As a result, the virus is engulfed. RNA and proteins are made and assembled into new virions.

LINK TO LEARNING

Click through this tutorial on viruses to identify structures, modes of transmission, replication, and more.

Viruses and Disease

Viruses cause a variety of diseases in animals, including humans, ranging from the common cold to potentially fatal illnesses like meningitis (Figure 11.7). These diseases can be treated by antiviral drugs or by vaccines, but some viruses, such as HIV, are capable of avoiding the immune response and mutating so as to become resistant to antiviral drugs.

The illustration shows an overview of human viral diseases. Viruses that cause encephalitis or meningitis, or inflammation of the brain and surrounding tissues, include measles, arbovirus, rabies, JC virus, and LCM virus. The common cold is caused by rhinovirus, parainfluenza virus, and respiratory syncytial virus. Eye infections are caused by herpesvirus, adenovirus, and cytomegalovirus. Pharyngitis, or inflammation of the pharynx, is caused by adenovirus, Epstein-Barr virus, and cytomegalovirus. Parotitis, or inflammation of the parotid glands, is caused by mumps virus. Gingivostomatitis, or inflammation of the oral mucosa, is caused by herpes simplex type I virus. Pneumonia is caused by influenza virus types A and B, parainfluenza virus, respiratory syncytial virus, adenovirus, and SARS coronavirus. Cardiovascular problems are caused by coxsackie B virus. Hepatitis is caused by hepatitis virus types A, B, C, D, and E. Myelitis is caused by poliovirus and HLTV-1. Skin infections are caused by varicella-zoster virus, human herpesvirus 6, smallpox, molluscum contagiosum, human papillomavirus, parvovirus B19, rubella, measles, and coxsackie A virus. Gastroenteritis, or digestive disease, is caused by adenovirus, rotavirus, norovirus, astrovirus, and coronavirus. Sexually transmitted diseases are caused by herpes simplex type 2, human papillomavirus, and HIV. Pancreatitis B is caused by coxsackie B virus.

Figure 17.7 Viruses are the cause of dozens of ailments in humans, ranging from mild illnesses to serious diseases. (credit: modification of work by Mikael Häggström)

Vaccines for Prevention

While we do have limited numbers of effective antiviral drugs, such as those used to treat HIV and influenza, the primary method of controlling viral disease is by vaccination, which is intended to prevent outbreaks by building immunity to a virus or virus family. A vaccine may be prepared using weakened live viruses, killed viruses, or molecular subunits of the virus. In general, live viruses lead to better immunity, but have the possibility of causing disease at some low frequency. Killed viral vaccine and the subunit viruses are both incapable of causing disease, but in general lead to less effective or long-lasting immunity.

Weakened live viral vaccines are designed in the laboratory to cause few symptoms in recipients while giving them immunity against future infections. Polio was one disease that represented a milestone in the use of vaccines. Polio epidemics occurred with increasing frequency and impact as the twentieth century progressed, becoming a terrifying and tragic event each summer. Tens of thousands of people died and many more were paralyzed; children made up a large portion of the victims. Using killed virus tested on the HeLa cell line (originally (unethically) obtained from Henrietta Lacks and then mass produced to meet the need), Jonas Salk developed a successful vaccine. Mass immunization campaigns in the U.S. in the 1950s (killed vaccine) and 1960s (live vaccine) essentially eradicated the disease. The success of the polio vaccine paved the way for the routine dispensation of childhood vaccines against measles, mumps, rubella, chickenpox, and other diseases.

Live vaccines are usually made by attenuation (weakening) of the “wild-type” (disease-causing) virus by growing it in the laboratory in tissues or at temperatures different from what the virus is accustomed to in the host. These attenuated viruses thus still cause an infection, but they do not grow very well, allowing the immune response to develop in time to prevent major disease. The danger of using live vaccines, which are usually more effective than killed vaccines, is the low but significant risk that these viruses will revert back to their disease-causing form. This happened as recently as 2007 in Nigeria where mutations in a polio vaccine led to an epidemic of polio in that country.

Some vaccines are in continuous development because certain viruses, such as influenza and HIV, have a high mutation rate compared to other viruses or host cells. With influenza, mutation in genes for the surface molecules helps the virus evade the protective immunity that may have been obtained in a previous influenza season, making it necessary for individuals to get vaccinated every year. Other viruses, such as those that cause the childhood diseases measles, mumps, and rubella, mutate so little that the same vaccine is used year after year.

Other vaccines are developed because of a new mutation of a well known type of virus. Coronaviruses are very common in nature and various diseases, but a specific mutation of a particular coronavirus led to the COVID-19 pandemic. The rapid development of successful vaccines was due in part to scientists who had been working with other coronaviruses prior to the pandemic. Kizzmekia S. Corbett, a research fellow and scientific lead, had deep experience and knowledge of coronaviruses, which was instrumental in developing one of the first vaccines (Moderna). She is now applying that experience to other respiratory diseases and vaccine development processes.

Vaccines and Antiviral Drugs for Treatment

Vaccines can sometimes be used to treat active viral infections, such as rabies and Ebola. With rabies, there’s a window of opportunity after a bite but before the virus reaches the central nervous system, during which vaccination can prevent the disease from becoming fatal. Similarly, for Ebola, which has a high mortality rate and spreads from animals like bats and great apes to humans, vaccines that strengthen the immune response are being used with the hope of reducing deaths. These vaccines work by preparing the immune system to fight off the virus more effectively.

Another way of treating viruses is through the use of antiviral drugs are used to manage symptoms and control viral infections, though they often can’t cure the virus completely. Gertrude Elion’s pioneering work led to targeted drugs that inhibit viral functions, like DNA replication, without harming the host’s cells. These drugs, including acyclovir for herpes and Tamiflu for influenza, help make symptoms more manageable rather than providing a cure. The most effective antiviral treatments have been against HIV, which, without treatment, is typically fatal within a decade. The use of highly active antiretroviral therapy (HAART), a combination of drugs targeting different stages of the HIV life cycle, has significantly extended the lives of those infected. However, due to the virus’s ability to mutate, ongoing research is crucial to stay ahead of drug resistance and continue the fight against this challenging virus.

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