All viruses are obligate intracellular parasites: they take over a host cells synthetic machinery in order to reproduce and be transmitted to other cells.

Size

Does size matter? According to the makers of the Godzilla movie, they would have you believe so! Viruses are measured in terms of nanometers (vary between 20-300 billionths of a meter). They are visible only with the aid of an electron microscope.

Classification

Viruses are not included in the 5 kingdom classification system of living organisms. In the 1930's viruses were named for the host organism that they infected: plant , animal or bacterium. Most viruses have not yet been classified due to lack of data concerning their reproduction and molecular biology. Many thousands of viruses are currently being studied worldwide. By 1995 over 4,000 viruses had been assigned to 71 virus families.Today virus classification is undergoing great changes. Viruses are typically classified according to:

• the nature of their genetic material
• symmetry and composition of their capsids

Viral structure

Viruses have been defined as "a piece of bad news wrapped up in protein." (Peter Medewar. Nobel Prize 1960, Physiology & Medicine). Not all virologists agree with this succinct description of a virus!

Nucleic acid (The bad news)

• Viruses have either DNA or RNA as their genetic material but never both.
• The nucleic acid is either double stranded or single stranded.
• Some viruses have separate strands of nucleic acid:
• influenza virus has 8 ssRNA molecules
• HIV has two identical RNA strands

Capsid

The nucleic acid is surrounded by a protein coat called a capsid. The capsid is composed of protein subunits which in turn, comprise building blocks of capsids known as capsomeres. Viruses are really admirable molecular architects. The capsid typically assumes a defined form of cubic symmetry whereby the virus has a number of axes about which it can be rotated and appears identical when viewed from a number of angles. As viruses typically only code for a limited number of proteins the repetitive nature of the capsid is really the only efficient way to build a shell. The organization of the capsid has proved a useful characteristic for classifying viruses into groups:

Polyhedron (many-sided capsids) are the preferred form in virus structure; the capsid is typically an icosahedron consisting of 20 identical equilateral triangular faces and 12 corners. Have you ever been into a geodesic dome? The architect, Buckminster Fuller, recognized the importance and energy-saving design of an icosahedron as he designed geodesic homes for human habitation. If you walked into one of these homes it would be analogous to entering a capsid (pretty cool huh?!)

Envelope

Some viruses are further enclosed by a lipid envelope which is acquired by budding out of the host cell membrane or by moving through a cells membrane system(s) such as the E.R. and golgi apparatus.

Some enveloped viruses have glycoprotein spikes that extend from the envelope which act to attach viruses to host cell receptors. Enveloped viruses are usually more fragile than nonenveloped (naked) viruses. Conditions that damage membranes will damage the envelope.

Viruses that lack an envelope are termed naked.

Historical Background

The outcome of viral infection has not always been viewed in a negative light. Consider the "Tulipomania" of the late 1500s to mid 1600s in Holland. "Color-breaking" in tulips (caused by viral infection) created fantastically beautiful flowers with variegated colors. These flowers were the subject matter of many a still life painted by Dutch Masters of the time. Maybe it was not so great for the tulip, but it was good for the artist's pocketbook!

1886: The first viral infection to be characterized was the tobacco mosaic virus (TMV). The German researcher, Adolf Mayer, ground up diseased leaves and reproduced the plant disease in healthy tobacco plants. He was unable to isolate the disease agent.

1898: The Dutch scientist, Beijerinck, passed fluid from leaves infected with TMV through porcelain filters which had pore sizes small enough to trap bacteria. Beijerinck was the first to make a connection between the filtrates and their infectious capability; he reasoned that some infectious agent, smaller than a bacterium must have been making the plants sick. Note that at this time, viruses as microbes were not known and the term "filterable disease agent" was used.

1898: the first filterable animal viral disease was isolated by Loeffler and Frosch which caused "Foot and Mouth Disease" of cattle.

1900. The first human disease known to be caused by a filterable agent was Yellow fever (a mosquito-transmitted disease) , recognized by the US Army under the direction of (Sir) Walter Reed.

1916/1917. Bacteriophages ( viruses that "eat bacteria") were independently recognized by the British researcher, Frederick Twort, and the French Researcher, Felix D'Herelle. The researchers noted the significance of plaque formation, whereby lysis of bacterial cells by phages would leave visible clearings on petri plates. Plaque formation is an important tool in "phage typing" or identification of specific bacterial strains. D'Herelle also recognized the significance of phage therapy. Humans could receive phages in order to treat specific bacterial infections. Research on phage therapy fell by the wayside as antibiotics became popular. However, as antibiotic resistance is a serious threat phage therapy is once again being considered as a realistic alternative to antibiotics.

The electron microscope became available in the late 1930's and for the first time viruses could be visualized. Negative staining techniques were also developed as powerful tools for analyzing viral particles.

As a science, the field of virology is a relatively young one. Once the structure of DNA and the nature of the genetic code was elucidated in the 1950's, rapid advances were made in understanding the molecular biology of viruses.

VIRAL REPLICATION

There are 5 major steps to viral replication:

• adsorption
• penetration
• biosynthesis
• maturation
• release

These steps differ somewhat between bacteriophages and animal viruses.

Bacteriophages: lytic cycle

Tail fibers of the phage act like landing gear for the virus; they attach to specific receptors on the surface of bacterium. The phage tail sheath retracts like a syringe to inject the nucleic acid into cell. The capsid is left behind. Bacterial DNA becomes disrupted and phage DNA takes over cell functions. Viral DNA is copied to mRNA by host cell enzymes and new viruses are packaged in the host cell cytoplasm. The bacterial cell wall is subject to lysis and newly synthesized viruses are released.

Bacteriophages: lysogenic cycle

Phages that are temperate live in a long-term stable relationship with their host rather than kill it outright. In this situation phage DNA integrates with the host cell DNA and forms a prophage. Viral DNA is replicated along with the bacterial DNA each time the cell divides. Viruses that carry genes for botulism and diphtheria toxins replicate in bacteria in this manner. From time to time the phage DNA can excise from the bacterium (it "senses" that it's time to find a new home) and undergo a lytic cycle. Viruses that transport genes from one bacterium to another do so by a process known as transduction.

REPLICATION OF ANIMAL VIRUSES

The major steps of animal virus replication are summarized as follows. (Note the differences between animal viruses and phage replication

• Host receptors are cell membrane proteins and glycoproteins The capsid penetrates the cytoplasm either by fusion (as with enveloped viruses such as HIV) to the cell membrane or by endocytosis.
• Uncoating is required whereby the capsid proteins are removed enzymatically
• Biosynthesis of viral particles occurs in the nucleus (DNA viruses) or the cytoplasm (RNA viruses).
• Many ssRNA viruses have positive (+) sense strand RNA; this functions directly as mRNA and can be translated into protein by host ribosomes.(example: Poliovirus)
• ssRNA viruses with a negative (-) antisense RNA genome must first transcribe a + sense strand that can function as mRNA before they can produce proteins (example: Rabies virus). The enzyme that produces a +RNA from a - strand is known as an RNA-dependent RNA polymerase.
• RNA viruses known as retroviruses, form a DNA copy from an RNA template using reverse transcriptase. This enzyme is an RNA-dependent DNA polymerase. Before transcription occurs, the viral DNA must be integrated into the host cell DNA. This stage is known as a provirus which, unlike a phage, does not excise from the host cell chromosome.
• With integrated viruses, a state of latency can exist, which is a hallmark of Herpes (DNA) virus infections. Latent viruses may be reactivated following immunosuppression or stress (note: there is no true viral latency with HIV).
• Integrated viruses may also be oncogenic (cause cancer) (see below).
• The route of release of mature virions depends on the presence or absence of an envelope. Enveloped viruses bud out of the host cell membrane; naked viruses rupture the cell membrane.

DOUBLE-STRANDED DNA VIRUSES

Virus Family	Envelope/Capsid Shape	Example(s)	Infection/Disease
Adenoviridae	Naked/Polyhedral	Adenoviruses	Respiratory infections (link with obesity?)
Herpesviridae	Enveloped/Polyhedral	alpha: HSV1/HSV2 Varicella-Zoster beta: Cytomegalovirus* gamma: Epstein Barr virus* HHV8*	oral/genital herpes Chickenpox/shingles CMV mononucleosis/cancers Kaposi's sarcoma
Poxviridae	Enveloped/Complex	Orthopoxvirus	Smallpox Cowpox (Vaccinia)
Papovaviridae	Naked/Polyhedral	Human papilloma viruses*	warts including genital warts
Hepadnaviridae	Enveloped/Polyhedral	Hepatitis B virus*	Hepatitis B

* Viruses with oncogenic (cancer-causing) potential. NOTE: Approximately 10% of human cancers are virus-induced.

* Viruses with oncogenic (cancer-causing) potential.