Viruses - OpenStax CNX · chimpanzees and palm civets and Egyptian fruit bats, as is the next...

OpenStax-CNX module: m47432 1

Viruses∗

Robert Bear

David Rintoul

Based on Viruses† by

OpenStax College

This work is produced by OpenStax-CNX and licensed under the

Creative Commons Attribution License 4.0‡

Introduction

That's the salubrious thing about zoonotic diseases: they remind us, as Saint Francis did, that

we humans are inseparable from the natural world. In fact, there is no "natural world", its a

bad and arti�cial phrase. There is only the world. Humankind is part of that world, as are the

ebolaviruses, as are the in�uenzas and the HIVs, as are Marburg and Nipah and SARS, as are

chimpanzees and palm civets and Egyptian fruit bats, as is the next murderous virus - the one

we haven't yet discovered.

David Quammen, Spillover: Animal Infections and the Next Human Pandemic, 2012

∗Version 1.8: Jul 26, 2014 5:23 pm -0500†http://cnx.org/content/m45541/1.3/‡http://creativecommons.org/licenses/by/4.0/

http://cnx.org/content/m47432/1.8/


Figure 1: (a) The tobacco mosaic virus, seen by transmission electron microscopy, was the �rst virus tobe discovered. (b) The leaves of an infected plant are shown. (credit a: scale-bar data from Matt Russell;credit b: modi�cation of work by USDA, Department of Plant Pathology Archive, North Carolina StateUniversity)

No one knows exactly when viruses emerged or from where they came, since viruses do not leave physicalevidence in the form of fossils. Modern viruses are thought to be a mosaic of bits and pieces of nucleic acidspicked up from various sources along their respective evolutionary paths. Viruses are acellular, parasiticentities that are not classi�ed within any of the three domains because they are not exactly alive. But theydo parasitize, evolve, reproduce and co-evolve with other organisms; they inhabit a shadowy world thatmay not be alive, but is very close to it. They have no plasma membrane, internal organelles, or metabolicprocesses, and they do not divide. Instead, they infect a host cell and use the host's replication processesto produce progeny virus particles. Viruses infect all forms of organisms including bacteria, archaea, fungi,plants, and animals.

Viruses are diverse. They vary in their structure, their replication methods, and in their target hosts oreven host cells. They infect every type of organism known, from Archaea to Bacteria to Eukaryotes, and arefound in every environment. They are also remarkably abundant; it is estimated that each milliliter of seawater contains 107 viruses, both DNA and RNA varieties. They are major players in the evolution of thelife forms on this planet; genes derived from viruses allowed mammals to develop a placenta, for example.

1 How Viruses Replicate

Viruses were �rst discovered after the development of a porcelain �lter, called the Chamberland-Pasteur�lter, which could remove all bacteria visible under the microscope from any liquid sample. In 1886, AdolphMeyer demonstrated that a disease of tobacco plants, tobacco mosaic disease, could be transferred from adiseased plant to a healthy one through liquid plant extracts. In 1892, Dmitri Ivanowski showed that thisdisease could be transmitted in this way even after the Chamberland-Pasteur �lter had removed all viablebacteria from the extract. Still, it was many years before it was proven that these ��lterable� infectiousagents were not simply very small bacteria but were a new type of tiny, disease-causing particle.

Virions, single virus particles, are very small, about 20�250 nanometers (1 nanometer = 1/1,000,000mm); although the recent discovery of entities called Pandoraviruses (approx 1 micrometer, or 1/1,000,000mm in diameter) has shaken that paradigm somewhat. Individual virus particles are the infectious form ofa virus outside the host cell. Unlike bacteria (which are about 100 times larger), we cannot see most viruseswith a light microscope, with the exception of the Pandoraviruses and some large virions of the poxvirus



family (Figure 2).

Figure 2: The size of a virus is very small relative to the size of cells and organelles.

It was not until the development of the electron microscope in the 1940s that scientists got their �rstgood view of the structure of the tobacco mosaic virus (Figure 1) and others. The surface structure of virionscan be observed by both scanning and transmission electron microscopy, whereas the internal structures ofthe virus can only be observed in images from a transmission electron microscope (Figure 3).



Figure 3: The ebola virus is shown here as visualized through (a) a scanning electron micrograph and(b) a transmission electron micrograph. (credit a: modi�cation of work by Cynthia Goldsmith, CDC;credit b: modi�cation of work by Thomas W. Geisbert, Boston University School of Medicine; scale-bardata from Matt Russell)

The use of this 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 classi�ed by the type of nucleic acid they contained, DNA or RNA, and whethertheir nucleic acid was single- or double-stranded. More recently, molecular analysis of viral replicationcycles has further re�ned their classi�cation. Currently virus classi�cation begins at the level of Order, andproceeds to species level taxonomy using this scheme. The terms in parentheses are the taxon su�xes forthat taxonomic level.

Virus classi�cation

• Order (-virales)• Family (-viridae)• Subfamily (-virinae)• Genus (-virus)• Species (usually XXXX (disease) virus, e.g., Tobacco Mosaic Virus)

A virion consists of a nucleic-acid core, an outer protein coating, and sometimes an outer envelope made ofprotein and phospholipids derived from the host cell. The most visible di�erence between members of viralfamilies is their morphology, which is quite diverse. An interesting feature of viral complexity is that thecomplexity of the host does not correlate to the complexity of the virion. Some of the most complex virionstructures are observed in bacteriophages, viruses that infect the simplest living organisms, bacteria.

Viruses come in many shapes and sizes, but these are consistent and distinct for each viral family(Figure 4). All virions have a nucleic-acid genome covered by a protective layer of protein, called a capsid.The capsid is made of protein subunits called capsomeres. Some viral capsids are simple polyhedral �spheres,�whereas others are quite complex in structure. The outer structure surrounding the capsid of some viruses is



called the viral envelope. All viruses use some sort of glycoprotein to attach to their host cells at moleculeson the cell called viral receptors. The virus exploits these cell-surface molecules, which the cell uses for someother purpose, as a way to recognize and infect speci�c cell types.

The T4 bacteriophage, which infects the E. coli bacterium, is among the most complex virions known;T4 has a protein tail structure that the virus uses to attach to the host cell and a head structure that housesits DNA.

Adenovirus, a nonenveloped animal virus that causes respiratory illnesses in humans, uses protein spikesprotruding from its capsomeres to attach to the host cell. Nonenveloped viruses also include those that causepolio (poliovirus), plantar warts (papillomavirus), and hepatitis A (hepatitis A virus). Nonenveloped virusestend to be more robust and more likely to survive under harsh conditions, such as the gut.

Enveloped virions like HIV (human immunode�ciency virus), the causative agent in AIDS (acquired im-mune de�ciency syndrome), consist of nucleic acid (RNA in the case of HIV) and capsid proteins surroundedby a phospholipid bilayer envelope and its associated proteins (Figure 4). Chicken pox, in�uenza, and mumpsare examples of diseases caused by viruses with envelopes. Because of the fragility of the envelope, nonen-veloped viruses are more resistant to changes in temperature, pH, and some disinfectants than envelopedviruses.

Overall, the shape of the virion and the presence or absence of an envelope tells us little about whatdiseases the viruses may cause or what species they might infect, but is still a useful means to begin viralclassi�cation.

Figure 4: Viruses can be complex in shape or relatively simple. This �gure shows three relativelycomplex virions: the bacteriophage T4, with its DNA-containing head group and tail �bers that attachto host cells; adenovirus, which uses spikes from its capsid to bind to the host cells; and HIV, which usesglycoproteins 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 reversetranscribes its RNA genome into DNA, which is then spliced into the host's DNA. (credit �bacteriophage,adenovirus�: modi�cation of work by NCBI, NIH; credit �HIV retrovirus�: modi�cation of work by NIAID,NIH)

Unlike all living organisms that use DNA as their genetic material, viruses may use either DNA or RNAas theirs. The virus core contains the genome or total genetic content of the virus. Viral genomes tend tobe small compared to bacteria or eukaryotes, containing only those genes that code for proteins the viruscannot get from the host cell. This genetic material may be single-stranded or double-stranded. It may alsobe linear or circular. While most viruses contain a single segment of nucleic acid, others have genomes thatconsist of several segments. All of these features are used to help classify viruses into orders, families, etc.

DNA viruses have a DNA core. The viral DNA directs the host cell's replication proteins to synthesizenew copies of the viral genome and to transcribe and translate that genome into viral proteins. DNA virusescause human diseases such as chickenpox, hepatitis B, and some venereal diseases like herpes and genital



warts.RNA viruses contain only RNA in their cores. To replicate their genomes in the host cell, the genomes

of RNA viruses encode enzymes not found in host cells. RNA polymerase enzymes are not as stable asDNA polymerases and often make mistakes during transcription. For this reason, mutations, changes in thenucleotide sequence, in RNA viruses occur more frequently than in DNA viruses. This leads to more rapidevolution and change in RNA viruses. For example, the fact that in�uenza is an RNA virus is one reason anew �u vaccine is needed every year; rapid evolution results in new �u strains being produced constantly invarious parts of the world. Human diseases caused by RNA viruses include hepatitis C, measles, and rabies.

1.1 Steps of Virus Infections

Viruses are specialized parasites, usually only infecting one type of cell or one type of organism. A virus must�take over� a cell to replicate. The viral replication cycle can produce dramatic biochemical and structuralchanges in the host cell, which may cause cell damage. These changes, called cytopathic e�ects, can changecell 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�), releasingall the progeny virions at once. The symptoms of these viral diseases result from the immune response tothe virus, which attempts to control and eliminate the virus from the body, and from cell damage causedby the virus. Many animal viruses, such as HIV (human immunode�ciency virus), leave the infected cellsof the immune system by a process known as budding, where virions leave the cell individually. During thebudding process, the cell does not undergo lysis and is not immediately killed. However, the damage to thecells that HIV infects may make it impossible for the cells to function as mediators of immunity, even thoughthe cells remain alive for a period of time. Most productive viral infections follow similar steps in the ,virusreplication cycle : attachment, penetration, uncoating, replication, assembly, and release.

A virus attaches to a speci�c receptor site on the host-cell membrane through attachment proteins inthe capsid or proteins embedded in its envelope. The attachment is speci�c, and typically a virus will onlyattach to cells of one or a few species and only certain cell types within those species with the appropriatereceptors.

The nucleic acid of bacteriophages is injected directly into the host cell, leaving the capsid outside the cell.Plant and animal viruses can enter their cells through endocytosis, in which the cell membrane surrounds andengulfs the entire virus. Some enveloped viruses enter the cell when the viral envelope fuses directly with thecell membrane. Once inside the cell, the viral capsid is degraded and the viral nucleic acid is released, whichthen becomes available for replication and transcription. Obviously, the naked DNA of a bacteriophage isalready available for transcription and replication immediately after being injected into the bacterial cell.

The replication mechanism depends on the viral genome (DNA or RNA). DNA viruses usually use hostcell proteins and enzymes to make additional DNA that is then used to copy the genome or be transcribed tomessenger RNA (mRNA). The mRNA is then used in protein synthesis. RNA viruses, such as the in�uenzavirus, usually use the RNA as a template for synthesis of viral genomic RNA and mRNA. The viral mRNAis translated into viral enzymes and capsid proteins to assemble new virions (Figure 5).

The last stage of viral replication is the release of the new virions into the host organism, where they areable to infect adjacent cells and repeat the replication cycle. Some viruses are released when the host celldies and other viruses can leave infected cells by budding through the membrane without directly killing thecell.



Figure 5: In in�uenza virus infection, glycoproteins attach to a host epithelial cell. As a result, thevirus is engulfed. RNA and proteins are made and assembled into new virions.

1.2 Lytic and Lysogenic Pathways

Cell death may be immediate or delayed after attachment and penetration by the virus. For example,bacteriophages, viruses that infect bacteria, may or may not kill their host immediately. There are two viralreplication strategies; when the virus kills the host cell it is called the lytic cycle, and when the virus doesnot kill the host but replicates when the host replicates it is called the lysogenic cycle (Figure 6).



Figure 6: The two viral reproductive strategies, the lytic cycle and the lysogenic cycle

Lytic cycle

The lytic cycle causes death of the host cell and the term refers to the last stage of the infection when thecell lyses (breaks open) and releases new virions that were produced within the cell. These new virions caninfect healthy cells and the cycle is repeated (Figure 6).

So why haven't all the bacteria in the world been destroy by bacteriophages? The answer is naturalselection of defense mechanisms by bacteria. Mutations of bacterial surface proteins that are not recognizedby a particular phage allow the bacteria to survive by preventing attachment. Without going into detail,bacteria have internal defenses that allow them to cut up viral DNA before it can infect the cell. Then onemight ask, why hasn't all the bacteriophages in the world gone extinct by not being able to reproduce. Onceagain, the answer is natural selection. Viruses mutate to bypass the defense mechanisms of the bacteria.This illustrates that the parasite-host relationship is in a constant evolutionary duel.Similar co-evolutionarystrategies characterize the interactions of viruses and animals, or viruses and plants.Lysogenic cycle

There is another reason why bacteria are not extinct because of bacteriophages. Many bacteriophages donot kill their host but coexist within their host, and when this occurs it is called the lysogenic cycle. Afterpenetration, the viral DNA or RNA can either be incorporated into the host DNA, or the viral genome canbe a self-replicating entity. Once this occurs, the viral genome is replicated along with the host cell's DNA,but the virus does not destroy the cell as it does in the lytic cycle (Figure 6). However, at some point the



viral genes are turned on and can trigger the virus to enter the lytic cycle and kill the host cell (Figure 6).Cell starvation or cell damage (e.g. from radiation) may trigger a lysogenic infection to turn into a lyticinfection thereby killing the host cell. The next generation of viruses, depending on the host cell condition,can use either of the viral replication strategies, lysogenic or lytic, on the next host.

2 Viruses and Disease

Viruses cause a variety of diseases in animals, including humans, ranging from the common cold to potentiallyfatal illnesses like meningitis (Figure 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 becomeresistant to antiviral drugs.

Figure 7: Viruses are the cause of dozens of ailments in humans, ranging from mild illnesses to seriousdiseases. (credit: modi�cation of work by Mikael Häggstrom)


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