The general phases in the life cycle of animal viruses are adsorption, penetration, synthesis, assembly, and release from the host cell. Viruses vary in the exact mechanisms of these processes, but we will use a simple animal virus to illustrate the major events (process figure 1).

Process Fig1. General features in the multiplication cycle of an enveloped animal virus. Using an RNA virus (rubella virus), the major events are outlined, although other viruses will vary in exact details of the cycle.

Adsorption and Host Range

 Quick Search Invasion begins when the virus encounters a susceptible host cell and adsorbs specifically to receptor sites on the cell membrane. The mem brane receptors that viruses attach to are usually glycoproteins the cell requires for its normal function. For example, the rabies virus affixes to receptors found on mammalian nerve cells, and the human immunodeficiency virus (HIV) attaches to the CD4 protein on certain white blood cells. The mode of attachment varies between the two general types of viruses. In enveloped forms, such as influenza virus and HIV, glycoprotein spikes bind to the cell membrane receptors. Viruses with naked nucleocapsids (adenovirus, for example) use surface receptors on their capsids that adhere to cell membrane receptors (figure2).

Fig2.  The mode by which animal viruses adsorb to the host cell membrane. (a) An enveloped coronavirus with prominent spikes. The configuration of the spike has a complementary fit for the ACE-2 receptor on human cells. The process in which the virus lands on the cell and plugs into receptors is termed docking. (b) An adenovirus has a naked capsid that adheres to its host cell by nestling surface molecules on its capsid into the receptors on the host cell’s membrane.

(a): Kateryna Kon/Shutterstock

Because a virus can invade its host cell only through making an exact fit with a specific host molecule, the range of hosts it can infect in a natural setting is limited. This limitation, known as the host range, can vary from one virus to another. For example, hepatitis B infects only liver cells of humans; the poliovirus infects primarily intestinal and nerve cells of primates (humans, apes, and monkeys); and the rabies virus infects nerve cells of most mammals. Cells that lack compatible virus receptors are resistant to adsorption and invasion by that virus. This explains why, for example, human liver cells are not infected by the canine hepatitis virus and why dog liver cells cannot host the human hepatitis A virus. It also explains why viruses usually have tissue specificities called tropisms for certain cells in the body. The hepatitis B virus targets the liver, and the mumps virus targets salivary glands. Many viruses can be manipulated in the laboratory to infect cells that they do not infect naturally, thus making it possible to cultivate them.

Penetration/Uncoating of Animal Viruses

For an animal virus to successfully infect a cell, it must penetrate the cell membrane of the host cell and deliver the viral nucleic acid into the host cell’s interior. How animal viruses do this varies with the type of virus and type of host cell, but most of them enter through one of two means, fusion or endocytosis. In the case of fusion, the viral envelope fuses directly with the host cell membrane, so it can occur only in enveloped viruses (process figure 3). Following attachment of the virus to host cell receptors, the lipids within the cell membrane and viral envelope rearrange, allowing the nucleocapsid to be moved to the cytoplasm of the cell. The mumps virus and HIV both enter the cell in this manner.

Process Fig3.  Modes of virus penetration: fusion versus endocytosis. Enveloped viruses may enter a cell in one of two ways. (a) Fusion of the viral envelope with the host cell membrane allows the nucleocapsid to be released into the cytoplasm. (b) Binding of viral spikes to receptors on the host cell triggers endocytosis. The nucleocapsid enters the host cell enclosed in a vesicle and is later released. Nonenveloped viruses, because they have no lipid membrane and cannot fuse with the cell membrane, always enter the cell via endocytosis. (a-b): McGraw Hill

In the endocytosis version of penetration, the virus can be either enveloped or naked (process figure 3b), and it is engulfed entirely into a vesicle called an endosome after its initial attachment. Once inside the cell, the virus is uncoated. This means that the vesicle membrane becomes altered so that the viral nucleocapsid or nucleic acid can be released into the cytoplasm. In some vi ruses the vesicle membrane fuses with the virus, and in other cases the vesicle membrane develops openings for the virus to leave. Endocytosis is used by the enveloped herpesviruses and the naked poliovirus.

Synthesis: Replication and Protein Production

The synthetic and replicative phases of animal viruses are highly regulated and extremely complex at the molecular level. Free viral nucleic acid exerts control over the host’s metabolism and synthetic machinery. How this control proceeds will vary, depending on whether the virus is a DNA or an RNA virus. In general, the DNA viruses (except poxviruses) enter the host cell’s nucleus and are replicated and assembled there. RNA viruses are replicated and assembled in the cytoplasm, with some exceptions.

Here we provide a brief overview of the process, using an RNA virus as a model. Almost immediately upon entry, the viral nucleic acid alters the genetic expression of the host and instructs it to synthesize the building blocks for new viruses. First, the RNA of the virus directs the synthesis of viral proteins (translation). Most viruses with positive-strand RNA molecules already contain the correct message for translation into proteins. Viruses with negative strand RNA molecules must first synthesize positive strand RNA, using the negative strand RNA as a template. Some viruses come equipped with the necessary enzymes for synthesis of viral components; others utilize those of the host. During the final phase, the host’s replication and synthesis machinery produces new RNA, proteins for the capsid, spikes, and viral enzymes.

Assembly of Animal Viruses: Host Cell as Factory

Toward the end of the cycle—during the assembly stage—mature virus particles are constructed from the growing pool of parts. In most instances, the capsid is first laid down as an empty shell that will serve as a receptacle for the nucleic acid strand. Electron micrographs taken during this time show cells with masses of viruses, often enclosed in packets (see figure 5a). One important event leading to the release of enveloped viruses is the insertion of viral spikes into the host’s cell membrane so they can be picked up as the virus buds off with its envelope, as discussed.

Release of Mature Viruses

To complete the cycle, assembled viruses leave their host in one of two ways. Nonenveloped and complex viruses that reach maturation in the cell nucleus or cytoplasm are released through cell lysis or rupturing. Enveloped viruses are liberated by budding or exocytosis2 from the cell membrane. During this process, the nucleocapsid binds to the membrane, which curves completely around it and forms a small pouch. Pinching off the pouch releases the virus with its envelope (figure 4). Budding of enveloped viruses causes them to be shed gradually, without the sudden destruction of the cell. For some viruses, rather than budding out of the cell, they bud into the endoplasmic reticulum or Golgi apparatus, obtaining their envelope as they enter the organelle. The SARS-CoV-2 virus obtains its envelope in this way, budding into a lysosome before being packaged for exit from the cell. Regardless of how the virus leaves, most active viral infections are ultimately lethal to the cell because of accumulated damage. Lethal damages include a permanent shut down of metabolism and genetic expression, destruction of cell membrane and organelles, toxicity of virus components, and re lease of lysosomes.

Fig4.  Maturation and release of enveloped viruses. (a) As an enveloped virus is budded off the membrane, it simultaneously picks up an envelope and spikes. (b) Human immunodeficiency virus (red) buds off the surface of an infected cell (blue). (a): McGraw Hill; (b): National Institute of Allergy and Infectious Diseases, NIH

The length of a multiplication cycle, from adsorption to lysis, varies to some extent, but it is usually measured in hours. A simple virus such as poliovirus takes about 8 hours; parvovirus takes 16 to 18 hours; and more complex viruses, such as herpesviruses, require 72 hours or more.

A fully formed, extracellular virus particle that is virulent and able to establish infection in a host is called a virion. The number of virions released by infected cells is variable, controlled by fac tors such as the size of the virus and the health of the host cell.

About 3,000 to 4,000 virions are released from a single cell infected with poxviruses, whereas a poliovirus-infected cell can release over 100,000 virions. If even a small number of these virions happens to meet other susceptible cells and infect them, the potential for viral proliferation is immense.

Visible Damage to the Host Cell

The short- and long-term effects of viral infections on animal cells are well documented. Cytopathic effects (CPEs) are defined as virus-induced damage to the cell that alters its microscopic appearance. Individual cells can become disoriented, undergo gross changes in shape or size, or develop intracellular changes (figure5a). It is common to note inclusion bodies, or compacted masses of viruses or damaged cell organelles, in the nucleus and cytoplasm (figure5b). Examination of cells and tissues for cytopathic effects has been a traditional tool for diagnosing viral infections that is usually supplemented with more specific serological and molecular methods. Table1 summarizes some prominent cytopathic effects associated with specific viruses. One very common CPE is the fusion of multiple host cells into a syncytium, a single large cell containing multiple nuclei. These syncytia are a result of some vi ruses’ ability to fuse together the membranes of several host cells. One virus (respiratory syncytial virus) is even named for this effect.

Fig5. Cytopathic changes in cells and cell cultures infected by viruses. (a) A multinucleate giant cell (center) infected with the measles virus (inset). (b) Multiple small, dark inclusions are clearly visible within the nuclei of cultured cells infected with the varicella-zoster virus (500×). (a and a inset): CDC; (b): Source: CDC

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مواضيع ذات صلة

 How Viruses Are Classified and Named

Viral Components: Capsids, Nucleic Acids, and Envelopes

The General Structure of Viruses: Size Range

HIV Infections in Humans: Laboratory Diagnosis

HIV Infections in Humans :Clinical Findings

HIV Infections in Humans : Pathogenesis and Pathology

Animal Lentivirus Systems

Classification of Lentiviruses

Viral DNA Is Integrated into the Host-Cell Genome in Some Nonlytic Viral Growth Cycles

Lytic Viral Growth Cycles Lead to Death of Host Cells

Viral Capsids Are Regular Arrays of One or a Few Types of Protein

Structure and Composition of Lentiviruses