What Is a Virus

What Is a Virus ?

Viruses have always been difficult to define. Recall in chapter 1 that Beijerinck thought the disease agent he called a virus was a contagious living fluid. Pasteur had originated the term "virus" in 1885. He took the name from the Latin for poison. By 1908 we knew that viruses could cause diseases of plants, animals and even humans. And by 1940 we had seen pictures of viruses taken through the transmission electron microscope. But what is a virus? Is it like a cell?

To be considered a cell, three criteria must be met. First, there needs to be a membrane serving as a boundary for the structure. Second, a fluid environment must exist, in which biochemical reactions occur, surrounded by the membrane. And third, there must be genetic information in the form of DNA. The DNA is arranged into one or more chromosomes and contains the information codes for the cell. Eukaryotic cells, like plants, animals, fungi and protists may have additional organelles inside the fluid environment. Prokaryotic cells, such as the bacteria, do not have these additional organelles. Does a virus meet the criteria for being a cell? If a virus does not qualify as a cell, it cannot be considered to be alive. The Cell Theory tells us that all living things are composed of one or more cells. The cell is the basic unit of life. Therefore, if a virus does not qualify as a cell, can we consider it a living thing? Can we call it an organism? Before we can answer these last few questions, we need to look at the structure of a typical virus and then the structure of the influenza virus.

A. Viral Basics

The structural parts which comprise a virus have been know since the 1930’s. Viruses continue to surprise us with their diversity and their unique solutions to the problems of survival. A virus contains a single type of nucleic acid, either DNA or RNA, never both. The DNA or RNA may be double or single-stranded. This core of nucleic acid is known as the viral genome and is covered by a protein coat called a capsid. The genetic information in the DNA or RNA has the codes for producing and assembling more viruses. The capsid is composed of protein subunits called capsomeres. Those viruses that consist only of a capsid and a nucleic acid are called nucleocapsids or naked viruses.

Some viruses have an additional outer covering called an envelope. The envelope is composed of phospholipids and glycoproteins in most viruses. You may remember that the cell membrane consists of phospholipids and glycoproteins. As new virus particles are being assembled and finally leave their host cell, they take some of the membrane materials from the host cell. The virus may also add some of its own glycoproteins to the envelope. Some of these may appear as spikes. A virus with an envelope, with or without spikes, is called an enveloped virus.

As you can see, viruses lack the structures we associate with cells. In addition, viruses have no metabolic machinery of their own. They cannot carry out any of the functions we associate with living things unless they are inside a host cell. Viruses use the raw materials and the metabolic machinery of their host cells to direct the production and assembly of new viruses. You could consider a virus an intracellular (within a cell) genetic parasite. Since viruses depend on their host cells for replication (making exact copies), viruses can be difficult to grow in the laboratory. In order to do research and testing on viruses, the viruses must be grown in animal cells, such as chicken eggs.

B. Structure of the Influenza Virus

The influenza virus is an enveloped virus. This envelope is composed mainly of a lipid bilayer and is lined with a type of protein known as matrix protein. This combination of lipids and protein is sometimes called the matrix protein membrane. The outer surface is covered with two types of spikes made of glycoproteins and embedded in the envelope. The first type is known as hemagglutinin or HA. The name refers to the fact that the influenza virus can attach to red blood cells and cause them to clump or agglutinate. This same HA protein is responsible for the attachment of the virus to the host cell and beginning the infection of the cell. The second type of glycoprotein spike is called neuraminidase or NA. As you can see by the -ase ending on its name, it's an enzyme. Its major job seems to be allowing the newly formed viruses to leave the host cell without sticking to each other or the host cell. There are about 4-5 times more HA proteins than NA proteins in the lipid envelope.

Electron Micrographs of Influenza Virus

There are three types of influenza viruses. Type A contains lots of subtypes and has been the major culprit in epidemics and pandemics in the last 100 years. Type B has been responsible for some regional level epidemics. Type C seldom creates major problems and is known only in humans. Neither Type B or Type C have any known subtypes. Differences in the three types of viruses are due to differences in the HA and NA proteins, the viral genetic information and the matrix protein.

C. Influenza Genomes

The influenza genomes for Types A and B consist of 8 separate single-stranded RNA segments containing 10 genes. Type C contains only 7 RNA segments. These RNA segments are coated by helical nucleo-proteins creating segments sometimes known as ribonucleoproteins(RNP. Recall that this combination of genome and protein covering is also known as the nucleocapsid. The nucleocapsid of influenza viruses is surrounded by an envelope. Each of the RNA segments has the code for one or more of the viral proteins. The table below provides our current understanding of the genes and their functions . The influenza virus is one of very few to have its genome in separate segments. This segmenting of the genome increases the likelihood that new genetic sequences will develop if two different strains of virus infect a cell at the same time. Gene segments from each of the strains may produce new combinations leading to a new strain of flu. On the positive side, laboratory duplication of the genome segments may lead to new vaccine strains.

Genes of Influenza A and Presumed Functions


PB2 gene

codes for a RNA polymerase involved in cap binding (sealing end of molecule); part of transcriptase


PB1 gene

codes for an RNA polymerase involved in elongation of the molecule; part of transcriptase


PA gene

codes for an RNA polymerase which may serve as a protease; part of transcriptase


HA gene

codes for hemagglutinin; 3 distinct hemagglutinins are found in human infections (H1, H2,H3); at least 9 others have been found in animal flu viruses


NP gene

codes for the nucleoproteins; Types A, B, and C have different nucleoproteins; part of transcriptase complex


NA gene

codes for neuraminidase; involved with release of virus from the host cell; two different neuraminidases have been found in human viruses (N1,N2); at least 7 others in other animals; e.g. chickens, pigs, ducks


M1 gene


M2 gene

matrix protein; different sections of the genetic code of the gene are read to produce the two proteins;

ion channel protein



NS1 gene

NS2 gene

codes for 2 different non-structural proteins whose function is still unknown; as above different sections of the code are used for each

Diagram of Genome Structure of Influenza Viruses

D. Naming Viral Strains

Type A subtypes are identified and named using a very specific system. The geographic location where the strain was first isolated is first >followed by a lab identification number which usually tells how many cases were identified and isolated. Third comes the year of discovery and finally, in parentheses, the type of HA and NA it possesses. A typical example might be A/Hong Kong/156/97/(H5N1). Another example is A/Singapore/6/86/(H1N1). Scientists need to know this information so that they can prepare an appropriate vaccine against the particular influenza virus strain causing this year’s outbreak.

E. Changes in the Viral Genome

The influenza virus is constantly changing through mutations and reassortments and recombinations. Different subtypes of influenza A are found in the environment each winter. Therefore, a new flu vaccine must be produced each year. There are two conditions that are frequently mentioned as the major reasons for the instability of the influenza virus.

First, small changes in the genetic sequence of the HA or NA genes will lead to a change in the amino acid sequence of the HA or NA proteins. These changes often occur because the influenza virus is an RNA virus. RNA viruses, with few exceptions, are constantly making "spelling errors" in their genetic sequences when they are being copied. The RNA copy editing process is flawed. This leads to new genetic sequences. New genetic sequences lead to new amino acids being put into place in a protein. This usually leads to a new protein or an altered protein. This series of continual changes is known as genetic drift. The HA protein plays a large role in stimulating immunity, thus changes in this protein may cause a loss of immunity to the virus. NA protein plays a very minor role in immunity.

A second condition, known as genetic shift, is an extension of the genetic drift. Continual small changes in the HA and NA proteins may accumulate and over time become major changes in the proteins. This may lead to production of new HA or NA proteins unlike any previously known. This would lead to new viral strains against which the population has no immunity. When two strains of virus infect a cell at the same time. the genetic information may not only be copied incorrectly, but it may also be reassorted or recombined in new ways. This also could lead to strains of virus that could cause major epidemics or pandemics because the population has no protection against these new strains.

Changes in different influenza genes can also create problems. The September 7, 2001 issue of Science magazine contains an article which described a change in the PB2 gene. Recall, from the table presented earlier, that PB2 is found on segment #1. Researchers tested A/Hong Kong/97/(H5N1) in mice and found, by a system of elimination, that the PB2 gene was responsible for giving the virus its potency. While unsure as to the exact function of the gene, scientists believe that it directs production of an enzyme that forces the host cell to make more viruses. This change in the PB2 gene is significant because it changed a form of chicken flu into a strain deadly to humans in Hong Kong in 1997.

F. Determination of New Vaccine Components

The World Health Organization (W.H.O.) makes the decision as to which strains of the virus to include in the new vaccine. They analyze information that is provided by W.H.O. laboratories in Atlanta, London, Melbourne and Tokyo. These labs observe the dominant strains that have been circulating the previous winter. They also look for evidence of new strains with the potential to spread, particularly if the current vaccines would not provide protection against these new strains. A new vaccine would normally contain three components, two subtypes of influenza A and one of influenza B.

In February 2002, W.H.O. announced that a new strain of influenza virus had been isolated. The strain, subtype A/(H1N2), appears to be a combination of two human subtypes that have been causing sickness for a number of years. This new strain most probably has arisen from the reassortment of genetic information in the subtypes, A/(H1N1 and H3N2). This new strain was identified in China in 1988/89, but there was no spread of the virus at that time. This new A/(H1N2) strain has been isolated from people in England, Wales, Israel and Egypt. Because this new subtype is a combination of genetic information from A/(H1N1) and A/(H3N2), people who have been previously vaccinated should have a high level of immunity. Even those individuals who have not been previously vaccinated should have some immunity since these strains have been around for a number of years.

The composition of the influenza vaccine for the 2002/03 season was announced by W.H.O. on February 6, 2002. This vaccine is designed to be used for the winter months in the Northern Hemisphere. The contents of the vaccine will include:

• an A/New caledonia/20/99 (H1N1)-like virus
• an A/Moscow/10/99 (H3N2)–like virus (the widely used vaccine strain is A/Panama/2007/99)

a B/Hong Kong/330/2001 – a B Victoria-like virus

The first two components are the same found in this past year’s vaccine. It is felt that they will provide good protection against this new strain. Recommendations for the vaccine that will need to be produced for the Southern Hemisphere will be made by W.H.O. in September 2002. This will then be the vaccine that will be used in May 2003 through October 2003 in the Southern Hemisphere.

How do viruses produce copies of themselves in our cells? Should I get vaccinated? Should everyone get vaccinated? Are there any dangers in getting vaccinated? These are a few of the questions that will be answered in future chapters.



References and Resources

electron micrographs of influenza virus

good diagram of structure of HA

Public Health Laboratory Service Bulletin

Diagram of Genome Structure of Influenza Viruses