VIRUSES

 

 

Discovery of viruses

 

1883-A. Meyer, a German scientist, demonstrated that TMV (tobacco mosaic disease) was contagious by spraying sap from infected plants onto healthy plants, which then developed the disease.  He was unable to identify a microbe that might cause the disease when he examined the sap under the microscope.

 

1890- D. Ivanosky, a Russian scientist, proposed that TMV disease was caused by a bacterium that was either too small to be trapped by a filter or that produced a filterable toxin.  Filtered sap to remove bacteria. Filtered sap still transmitted disease.

 

1897-Martinus Beijerinck, a Dutch microbiologist, proposed that the disease was caused by a reproducing particle much smaller and simpler than bacteria.  He infected a series of plants with sap over several generations.  He concluded that the pathogen must have been reproducing because its ability to infect was undiluted by transfers from plant to plant.  He also noted that unlike bacteria, the pathogen 1) reproduced only within the host it infected.  2) Could not be cultured on media 3) could not be killed by alcohol.

 

1935-Wendell M. Stanley, an American biologist, crystallized the infectious particle now known as tobacco mosaic virus.

 

Composition of Viruses

 

In the 1950’s, the electron microscope allowed scientists to view the structure of viruses.

Viruses may range from 20-to100 nm.

 

1)     Viral Genomes

Depending upon the virus, viral genomes:

a)     May be double-stranded DNA, single-stranded DNA, double stranded RNA or Single stranded RNA.

b)    Are organized as single nucleic acid molecules that are either linear or circular.

c)    May have as few as four genes or as many as several thousand.

 

2)     Capsids and Envelopes

 

a)     Capsid- Protein coat that encloses the viral genome.

1)     Its structure may be rod-shaped, polyhedral or complex.

2)     Composed of many capsomeres-protein subunits made from only one or a few types of proteins.

 

b)    Envelope-Membrane that cloaks some viral capsids.

1)     Helps viruses infect their host.

2)     Derived from host cell membrane, which is usually virus-modified and contains proteins and glycoproteins of viral origin.

 

Viral Reproduction

 

Viruses are obligate intracellular parasites, which can express their genes and reproduce only within a living cell.  Each virus has a specific host range.

 

Host Range- Limited number or range of host’s cells that a parasite can infect.

1)     Viruses recognize host cells by a complimentary fit between viral proteins and specific cell surface sites.

2)     Some viruses have broad host ranges, which may include several species ( ex. Rabies).

3)     Some viruses have host ranges so narrow that they can:

a)     infect only one species.

b)    Infect only a single tissue type of one species. AIDS-T lymphocytes and macrophages.

 

Viral Life Cycle involves:

1)     Infecting the host cell with the viral genome.

2)     Coopting host cell’s resources to replicate the viral genome and manufacture capsid protein.

3)     Assembling newly produced viral nucleic acid and capsomeres into the next generation.

 

 

 

Methods of Infection of Host cells:

1)     Tailpiece to inject Nucleic acid into the host cell.

2)      Attach to membrane proteins to form portal.

 

Patterns of Viral Genome Replication:

1)     DNA—DNA.  If viral DNA is double-stranded, DNA replication resembles that of cellular DNA, and the virus uses DNA polymerase produced by the host.

2)     RNA—RNA.  Since host cells lack the enzyme to copy RNA, most RNA viruses contain a gene that codes for RNA replicase, an enzyme that uses viral RNA as a template to produce complimentary RNA.

3)     RNA—DNA.  Some RNA viruses encode reverse transcriptase, an enzyme that transcribes DNA from an RNA template.

 

Virus cells use the host cell’s enzymes, ribosome’s, tRNA’s, amino acids, ATP, and other resources to make copies of the viral genome and produce viral capsid proteins.

 

 

Reproductive Cycles of Bacteriophages:

 

I.      Lytic Cycle-A viral replication cycle that results in the death or lysis of the host cell.

 

1)     Phage attaches to cell surface.

2)     Phage contracts sheath and injects nucleic acid.

3)     Hydrolytic enzymes destroy host cell’s DNA.

4)     Phage genome directs the host cell to produce phage components-nucleic acid and capsid proteins.

5)     Cell lyses releases phage particles.

 

II.   Lysogenic cycle-A viral replication cycle that involves the incorporation of the viral genome into the host cell genome.

 

1)     Phage binds to surface of cell.

2)     Phage injects it nucleic acid into the host cell.

3)     Viral nucleic acid forms a circle and either begins a lytic cycle or a lysogenic cycle.

4)     During a lysogenic cycle the viral nucleic acid inserts by genetic recombination into a specific site on the hosts chromosome and becomes a prophage.

Prophage- a phage genome that is incorporated into a specific site on the bacterial chromosome.

a)     Most phage genes are inactive.

b)    Prophage genes are copied along with cellular DNA when the host cell reproduces.  As the cell divides, both prophage and cellular DNA are passed on to daughter cells.

c)     A prophage may be carried in the host’s chromosomes for many years (latent period).

 

5)     Occasionally a prophage may leave the chromosome.

a)     This may be spontaneous or caused by environmental factors such as radiation.

b)    The excision process may begin the phages lytic reproductive cycle.

c)     Virions produced during the lytic cycle may begin either a lytic or lysogenic cycle in their new host cells.

 

                               6) Some prophage genes in a lysogenic cell may be

                                    expressed and change the cell’s phenotype in a

                                     process called lysogenic conversion.  This occurs in          

         bacteria that cause diphtheria, botulism, and scarlet

         fever. Pathogenicity results from toxins coded for

         by prophage genes.

 

 

 

REPRODUCTIVE CYCLE OF ANIMAL VIRUSES:

 

I. Viruses with envelopes-some viruses are surrounded by a membranous envelope, which is unique to several groups  of animal viruses.  This envelope is:

1)    Outside the capsid and helps the virus enter the host cell.

2)    A lipid bilayer with glycoprotein spikes protruding from the outer surface.

 

A.   Replication cycle characterized by:

1)     Attachment-Glycoprotein spikes protruding from the viral envelope attach to receptor sites on the hosts plasma membrane.

2)     Entry-As the envelope fuses with the plasma membrane, the entire virus (capsid and genome) is transported into the cytoplasm by receptor-mediated endocytosis.

3)     Uncoating- Cellular enzymes uncoat the genome by removing the protein capsid from viral RNA.

4)     Viral RNA and Protein Synthesis;

a)     Some viral RNA polymerase is packaged in the virion.

b)    Viral RNA polymerase(transcriptase) replicates the viral genome and transcribes viral mRNA.

c)     Viral mRNA is translated into viral proteins including:

        Capsid proteins synthesized in free   

         ribosome’s.

                                                       Viral envelope glycoproteins synthesized

                                                        By ribosomes bound the the ER.  Sent to  

                                                       Golgi Apparatus for processing.Golgi

                                                       Vesicle transport glycoproteins to the

                                                         Plasma membrane, where they cluster

                                                          viral exit sites.

                                

                                 5)  Assembly and release-New capsids surround

                                       viral genomes.  Assembled virions envelop with

                                       the host plasma membrane as they bud off

                                       from the cells surface.

                                       Some envelopes such as those of the herpesvirus,

                                       a DNA virus, contain envelopes derived from the

                                       hosts cell’s  nuclear membrane. These reproduce

                                        within the host cell’s nucleus.  They may

                                        integrate their DNA into the cell’s genome

                                        as a provirus.

 

 

 

III.RNA Viruses:

 

Retroviruses-use reverse transcriptase to transcribe DNA from the viral RNA genome.  Most complicated reproductive cycle.

 

1)     Attachment and entry of the virion.

2)     Uncoating of single stranded RNA genome.

3)     Reverse transcription-Viral RNA is the template to produce DNA-the template for complementary DNA strand.

4)     Integration-Newly produced double-stranded viral DNA enters the nucleus.  Viral DNA inserts into chromosomal DNA and becomes a provirus (latent period).

5)     Viral RNA and protein synthesis-Proviral DNA is transcribed into mRNA and is translated into proteins.  Transcribed RNA may provide genomes for the next viral generation.

6)     Capsid assembly and release of new virions.

 

EVOLUTION OF VIRUSES:

Viruses are obligate intracellular parasites and cannot reproduce independently but they have a genome with the same genetic code a living organisms and they can mutate and evolve. 

Viruses probably evolved after the first cells, from fragments of cellular nucleic acid that were mobile genetic elements (escaped genes).

Evidence:

1.     Genetic material of different viral families is more similar to host genomes than to that of other viral families.

2.     Some viral genes are identical to cellular genes.

3.     Viruses of eukaryotes are more similar in genomic structure to their cellular hosts than to bacterial viruses.

4.     Viral genomes are similar to certain cellular genetic elements such as plasmids and transposons, all are mobile genetic elements.

 

 

 

VIRAL DISEASES:

Papovirus-warts

Herpesvirus-Simplex I-cold sores

                     Simplex II-genital sores

                     Varicella zoster- chicken pox, shingles

                      Epstein Barr virus-mononucleosis

Poxvirus-Small pox, vaccinia, cowpox

Picornovirus-Poliovirus,rhinovirus (common cold)

Togovirus-Rubella virus,yellow fever virus

Rhabdovirus-rabies

Paramyoxovirus-measles, mumps

Othomyxovirus-influenza

 

VACCINES

 

ANTIVIRAL DRUGS