Steps of Virus Infections

A virus must use cell processes 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 (causing cell damage) effects, can change cell functions or even destroy the cell. Some infected cells, such as those infected by the common cold virus known as rhinovirus, die through lysis (bursting) or apoptosis (programmed cell death), releasing all 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 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 the virus infects may make it impossible for the cells to function normally, even though the cells remain alive for a period of time. Most productive viral infections follow similar steps in the virus replication cycle: attachment, penetration, uncoating, replication, assembly, and release (Figure 21.8).

Attachment

A virus attaches to a specific receptor site on the host cell membrane through attachment proteins in the capsid or via glycoproteins embedded in the viral envelope. The specificity of this interaction determines the host—and the cells within the host—that can be infected by a particular virus. This can be illustrated by thinking of several keys and several locks, where each key will fit only one specific lock.

Link to Learning

This video explains how influenza attacks the body.

The video shows how viruses replicate in our body. Using the terminology provided in the video, explain how a virus attaches to a cell in our body?

1. When the virus capsule makes contact with the cell, it bursts, and then the virions attach to the cell.
2. If a key on the virus fits a lock on the surface of the cell, the virus will attach to the cell.
3. The keys automatically attach to all the locks.
4. The welcoming committee interlocks with the virus.

Egress

The last stage of viral replication is the release of the new virions produced in the host organism, where they are able to infect adjacent cells and repeat the replication cycle. As you’ve learned, some viruses are released when the host cell dies, and other viruses can leave infected cells by budding through the membrane without directly killing the cell.

Visual Connection

Figure 21.8 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.

Influenza virus is packaged in a viral envelope that fuses with the plasma membrane. This way, the virus can exit the host cell without killing it. What advantage does the virus gain by keeping the host cell alive?

1. The virus can live dormant in the host cell.
2. The virus capsid is upgraded.
3. Lysis causes the host cell to die.
4. The host cell can continue to make new virus particles.

Link to Learning

Visit this website to learn about viral replication.

How do viruses get inside a host cell?

1. To get inside the host cell, the virus forces the cell to lyse, or break open.
2. To get inside a host cell, he virus produces proteins and copies its genome.
3. To get inside a host cell, the virus attaches to a specific receptor site on the host cell.
4. To get inside a host cell, the virus can fuse the membrane of the cell.

Bacteriophages

Figure 21.9 This transmission electron micrograph shows bacteriophages attached to a bacterial cell. (credit: modification of work by Dr. Graham Beards; scale-bar data from Matt Russell)

Bacteriophages are viruses that infect bacteria (Figure 21.9). When infection of a cell by a bacteriophage results in the production of new virions, the infection is said to be productive. If the virions are released by bursting the cell, the virus replicates by means of a lytic cycle (Figure 21.10). An example of a lytic bacteriophage is T4, which infects Escherichia coli found in the human intestinal tract. Sometimes, however, a virus can remain within the cell without being released. For example, when a temperate bacteriophage infects a bacterial cell, it replicates by means of a lysogenic cycle (Figure 21.10), and the viral genome is incorporated into the genome of the host cell. When the phage DNA is incorporated into the host cell genome, it is called a prophage. An example of a lysogenic bacteriophage is the λ (lambda) virus, which also infects the E. coli bacterium. Viruses that infect plant or animal cells may also undergo infections where they are not producing virions for long periods. An example is the animal herpesviruses, including herpes simplex viruses, the cause of herpes in humans. In a process called latency, these viruses can exist in nervous tissue for long periods of time without producing new virions, only to leave latency periodically and cause lesions in the skin where the virus replicates. Even though there are similarities between lysogeny and latency, the term lysogenic cycle is usually reserved to describe bacteriophages. Latency will be described in more detail below.

Visual Connection

Figure 21.10 A temperate bacteriophage has both lytic and lysogenic cycles. In the lytic cycle, the phage replicates and lyses the host cell. In the lysogenic cycle, phage DNA is incorporated into the host genome, where it is passed on to subsequent generations. Environmental stressors such as starvation or exposure to toxic chemicals may cause the prophage to excise and enter the lytic cycle.

Which of the following statements is false?

1. In the lytic cycle, new phage are produced and released into the environment.
2. An environmental stressor can cause the phage to initiate the lysogenic cycle.
3. In the lysogenic cycle, phage DNA is incorporated into the host genome.
4. Bacteriophage is a viruses that infects bacteria.

Animal Viruses

Animal viruses, unlike the viruses of plants and bacteria, do not have to penetrate a cell wall to gain access to the host cell. Nonenveloped or naked animal viruses may enter cells in two different ways. As a protein in the viral capsid binds to its receptor on the host cell, the virus may be taken inside the cell via a vesicle during the normal cell process of receptor-mediated endocytosis. An alternative method of cell penetration used by nonenveloped viruses is for capsid proteins to undergo shape changes after binding to the receptor, creating channels in the host cell membrane. The viral genome is then injected into the host cell through these channels in a manner analogous to that used by many bacteriophages. Enveloped viruses also have two ways of entering cells after binding to their receptors: receptor-mediated endocytosis, or fusion. Many enveloped viruses enter the cell by receptor-mediated endocytosis in a fashion similar to some nonenveloped viruses. On the other hand, fusion only occurs with enveloped virions. These viruses, which include HIV among others, use special fusion proteins in their envelopes to cause the envelope to fuse with the plasma membrane of the cell, thus releasing the genome and capsid of the virus into the cell cytoplasm.

After making their proteins and copying their genomes, animal viruses complete the assembly of new virions and exit the cell. Enveloped animal viruses may bud from the cell membrane as they assemble themselves, taking a piece of the cell’s plasma membrane in the process. On the other hand, nonenveloped viral progeny, such as rhinoviruses, accumulate in infected cells until there is a signal for lysis or apoptosis, and all virions are released together.

As you will learn in the next module, animal viruses are associated with a variety of human diseases. Some of them follow the classic pattern of acute disease, where symptoms get increasingly worse for a short period followed by the elimination of the virus from the body by the immune system and eventual recovery from the infection. Examples of acute viral diseases are the common cold and influenza. Other viruses cause long-term chronic infections, such as the virus causing hepatitis C, whereas others, like herpes simplex virus, only cause intermittent symptoms. Still other viruses, such as human herpesviruses 6 and 7, which in some cases can cause the minor childhood disease roseola, often successfully cause productive infections without causing any symptoms at all in the host, and thus we say these patients have an asymptomatic infection.

In hepatitis C infections, the virus grows and reproduces in liver cells, causing low levels of liver damage. The damage is so low that infected individuals are often unaware that they are infected, and many infections are detected only by routine blood work on patients with risk factors. On the other hand, since many of the symptoms of viral diseases are caused by immune responses, a lack of symptoms is an indication of a weak immune response to the virus. This allows for the virus to escape elimination by the immune system and persist in individuals for years, all the while producing low levels of progeny virions in what is known as a chronic viral disease.

As already discussed, herpes simplex virus can remain in a state of latency in nervous tissue for months, even years. As the virus hides in the tissue and makes few if any viral proteins, there is nothing for the immune response to act against, and immunity to the virus slowly declines. Under certain conditions, including various types of physical and psychological stress, the latent herpes simplex virus may be reactivated and undergo a lytic replication cycle in the skin, causing the lesions associated with the disease. Once virions are produced in the skin and viral proteins are synthesized, the immune response is again stimulated and resolves the skin lesions in a few days by destroying viruses in the skin. As a result of this type of replicative cycle, appearances of cold sores outbreaks only occur intermittently, even though the viruses remain in the nervous tissue for life. Latent infections are common with other herpesviruses as well, including the varicella-zoster virus that causes chickenpox. After having a chickenpox infection in childhood, the varicella-zoster virus can remain latent for many years and reactivate in adults to cause the painful condition known as shingles (Figure 21.11ab).

Figure 21.11 (a) Varicella-zoster, the virus that causes chickenpox, has an enveloped icosahedral capsid visible in this transmission electron micrograph. Its double-stranded DNA genome becomes incorporated in the host DNA and can reactivate after latency in the form of (b) shingles, often exhibiting a rash. (credit a: modification of work by Dr. Erskine Palmer, B. G. Martin, CDC; credit b: modification of work by rosmary/Flickr; scale-bar data from Matt Russell)

Some animal-infecting viruses, including the hepatitis C virus discussed above, are known as oncogenic viruses: They have the ability to cause cancer. These viruses interfere with the normal regulation of the host cell cycle either by either introducing genes that stimulate unregulated cell growth (oncogenes) or by interfering with the expression of genes that inhibit cell growth. Oncogenic viruses can be either DNA or RNA viruses. Cancers known to be associated with viral infections include cervical cancer caused by human papillomavirus (HPV) (Figure 21.12), liver cancer caused by hepatitis B virus, T-cell leukemia, and several types of lymphoma.

Figure 21.12 HPV, or human papillomavirus, has a naked icosahedral capsid visible in this transmission electron micrograph and a double-stranded DNA genome that is incorporated into the host DNA. The virus, is oncogenic and can lead to cervical cancer. (credit: modification of work by NCI, NIH; scale-bar data from Matt Russell)

Link to Learning

Visit the interactive animations showing the various stages of the replicative cycles of animal viruses and click on the flash animation links.

Before a virus can replicate in a host cell, the capsid or envelope must be released. This process is sometimes referred to as ________.

1. viral attachment or adsorption
2. viral entry
3. uncoating
4. viral replication

Plant Viruses

Plant viruses, like other viruses, contain a core of either DNA or RNA. You have already learned about one of these, the tobacco mosaic virus. As plant viruses have a cell wall to protect their cells, these viruses do not use receptor-mediated endocytosis to enter host cells as is seen with animal viruses. For many plant viruses to be transferred from plant to plant, damage to some of the plants’ cells must occur to allow the virus to enter a new host. This damage is often caused by weather, insects, animals, fire, or human activities like farming or landscaping. Additionally, plant offspring may inherit viral diseases from parent plants. Plant viruses can be transmitted by a variety of vectors, through contact with an infected plant’s sap, by living organisms such as insects and nematodes, and through pollen. When plants viruses are transferred between different plants, this is known as horizontal transmission, and when they are inherited from a parent, this is called vertical transmission.

Symptoms of viral diseases vary according to the virus and its host (Table 21.4). One common symptom is hyperplasia, the abnormal proliferation of cells that causes the appearance of plant tumors known as galls. Other viruses induce hypoplasia, or decreased cell growth, in the leaves of plants, causing thin, yellow areas to appear. Still other viruses affect the plant by directly killing plant cells, a process known as cell necrosis. Other symptoms of plant viruses include malformed leaves, black streaks on the stems of the plants, altered growth of stems, leaves, or fruits, and ring spots, which are circular or linear areas of discoloration found in a leaf.

Plant viruses can seriously disrupt crop growth and development, significantly affecting our food supply. They are responsible for poor crop quality and quantity globally, and can bring about huge economic losses annually. Others viruses may damage plants used in landscaping. Some viruses that infect agricultural food plants include the name of the plant they infect, such as tomato spotted wilt virus, bean common mosaic virus, and cucumber mosaic virus. In plants used for landscaping, two of the most common viruses are peony ring spot and rose mosaic virus. There are far too many plant viruses to discuss each in detail, but symptoms of bean common mosaic virus result in lowered bean production and stunted, unproductive plants. In the ornamental rose, the rose mosaic disease causes wavy yellow lines and colored splotches on the leaves of the plant.