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Lecture notes: Introduction to Virology

Introduction

Viruses contribute significantly to the global burden of infectious disease.
We experience countless infections throughout their lives, with particularly high frequency in early childhood. While most of these are mild, viruses may cause severe disease in susceptible individuals, such as the mal-nourished, immuno-compromised, the very old and the very young. Recent years have also seen the emergence of new viral diseases such as HIV, SARS and "swine flu" (H1N1 pandemic influenza A).

What is a virus?
Viruses are uniquely different from the many uni-cellular micro-organisms you have studied so far. Protozoa, yeasts, bacteria, mycoplasmas, rikettsiae and chlamydiae are all living organisms with the following features in common:

  • They are all cells
  • They store their genetic information as DNA
  • Within their cell, they contain all the organelles necessary for producing energy and synthesizing proteins, carbohydrates, cell wall structures etc.
  • Replicate by means of binary fission

Viruses do not share these properties. They are not cells. They are very simple structures consisting essentially of a nucleic acid genome, protected by a shell of protein. They are metabolically inert and can only replicate once they are inside a host cell.

The genome consists of only one type of nucleic acid: either RNA or DNA. Most DNA viruses are double stranded and most RNA viruses have a single stranded (ss) genome. A ssRNA genome may be either positive sense (this means that it can be used as mRNA to make proteins) or negative sense. Negative sense RNA is complimentary to mRNA, in other words, it has to be copied into mRNA. The viral genome codes only for the few proteins necessary for replication: some proteins are non-structural e.g. polymerase and some are structural, i.e. they form part of the virion structure.

They have no organelles.

They are very small, sizes range from 20 to 200 nm. This is beyond the resolving power of the light microscope.

Terminology:

Virion = virus particle

Capsid = protein shell which surrounds and protects the genome. It is built up of multiple (identical) protein sub-units called capsomers. Capsids are either icosahedral or tubular in shape

Nucleocapsid = genome plus capsid

Envelope = lipid membrane which surrounds some viruses. It is derived from the plasma membrane of the host cell.

Peplomers = proteins found in the envelope of the virion. They are usually glycosylated and are thus more commonly known as glycoproteins.

Viral replication:

Viruses are the ultimate parasite. They are totally dependent on a host cell to replicate (make more copies of itself). While the sequence of events varies somewhat from virus to virus, the general strategy of replication is similar:

Adsorption: The surface of the virion contains structures that interact with molecules (receptors) on the surface of the host cell. This is usually a passive reaction (not requiring energy), but highly specific. It is the specificity of the reaction between viral protein and host receptor that defines and limits the host species and type of cell that can be infected by a particular virus. Damage to the binding sites on the virion or blocking by specific antibodies (neutralization) can render virions non-infectious.

Uptake: The process whereby the virion enters the cell. It occurs either as a result of fusion of the viral envelope with the plasma membrane of the cell or else by means of endocytosis.

Uncoating: Once inside the cell, the protein coat of the virion dissociates and the viral genome is released into the cytoplasm.

Early phase
Once the genome is exposed, transcription of viral mRNA and translation of a number of non-structural ("early") proteins takes place. The function of these is to replicate the viral genome.

Genome replication
Multiple copies of the viral genome are synthesized by a viral polymerase (one of the "early" proteins).

Late phase
Transcription and translation of viral mRNA and synthesis of the structural ("late") proteins which are needed to make new virions.

Assembly of new virions
Assembly of new viral capsids takes place either in the nucleus (e.g. herpesviruses) or in the cytoplasm (e.g. poliovirus) of the cell, or sometimes, just beneath the cell surface (e.g. budding viruses such as influenza). The proteins self assemble and a genome enters each new capsid.

Release of progeny virions
Release of new infectious virions is the final stage of replication. This may occur either by budding from plasma membrane or else by disintegration (lysis) of the infected cell. Some viruses use the secretory pathway to exit the cell: virus particles enclosed in golgi-derived vesicles are released to the outside of the cell when a transport vesicle fuses with the cell membrane.

How do viruses cause disease?

Viruses are capable of infecting all types of living organism from bacteria to humans, (including plants and insects!). A major factor that controls which cell type a virus can infect (cell tropism) is the presence (on the cell surface) of the appropriate receptor, to which the virus must attach in order to gain entry into the cell.

Viruses enter the body by inhalation, ingestion, sexual intercourse or inoculation through the skin or mucous membranes. Infection may also sometimes be passed from a mother to her foetus transplacentally (vertical transmission). Once a virus has gained entry into the body, infection may either remain localised to the site of entry (an example of this is influenza where the virus remains confined to the respiratory tract), or it may cause a disseminated infection. Here, the virus replicates initially at the site of entry, but then enters the blood (viraemia) or lymphatics and spreads throughout the body (e.g. Measles). Other viruses such as Rabies and Herpes Simplex may replicate locally initially, then enter nerve endings and travel up the axon to infect the central nervous system.

The term incubation period defines the time from exposure to an organism to the onset of clinical disease. In general, viruses that cause localized infections have short incubation periods (<7 days), while in disseminated infections, the incubation period tends to be longer.

Both viral and host factors contribute to clinical disease during the course of a viral infection. Host immune cells release interferons and other cytokines which induce the symptoms of fever and malaise. Tissue specific damage may be due to virus-induced lysis of infected cells or due to inflammation and destruction of infected cells by the host's immune response. Because viruses replicate intra-cellularly, recovery from a viral infection requires the action of specific cyto-toxic T lymphocytes which recognise and eliminate virus-infected cells. Virus-specific antibody levels rise during the course of the infection, but antibody plays only a limited role in recovery from an established infection for most viruses. Nonetheless specific antibody plays a very important role in preventing re-infection of the host with the same virus.

An effective immune response can eliminate most viruses from the body and thus most viral infections are short lived. However, there are certain viruses that are able to evade the immune response and establish persistent infections in their host. The most famous example of such a virus is HIV, but there are many others. Viruses use a variety of strategies to evade the immune system. On the whole, these persistent infections are asymptomatic and only manifest clinically if the patient becomes immuno-compromised.

Viruses and cancer:

About 15% of human cancers are caused by viruses. Certain persistent viruses survive in the host by transforming the cells they infect (inducing infected cells to proliferate). However, the virus infection is only the first step in the pathway to malignancy and only a small percentage of infected people actually get cancer.

Common virus-induced cancers include: carcinoma of the cervix (Human papillomavirus), liver cancer (hepatitis B and C), Kaposi sarcoma (human herpesvirus 8) and Burkitts lymphoma (Epstein Bar virus).

Disinfection and inactivation of viruses:

Heat Most are inactivated at 56 °C for 30 minutes or at 100 °C for a few seconds
Drying Variable; enveloped viruses are rapidly inactivated.
Ultra-violet irradiation Inactivates viruses
Organic solvents (Chloroform, Ether, Alcohol) Enveloped viruses are inactivated; those without are resistant.
Oxidizing and reducing agents Viruses are inactivated by formaldehyde, chlorine, iodine and hydrogen peroxide
Phenols Most viruses are resistant

 

 


 



 

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