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Productive Life Cycle of Animal Viruses Animations

  • Authors: Gary Kaiser 1, Erica Suchman 2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Biology Department, The Community College of Baltimore County, Catonsville Campus, Baltimore, MD, 21228; 2: Colorado State University, Fort Collins, Colorado, 80523
  • Citation: Gary Kaiser, Erica Suchman. 2008. Productive life cycle of animal viruses animations.
  • Publication Date : September 2008
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Introduction

Viruses are acellular and lack the metabolic machinery necessary for independent replication. They are, therefore, dependent upon their host cell for replication. The following steps represent the generalized productive life cycle for animal viruses:

1. Viral attachment or adsorption to the host cell



2. Viral entry into a cell



3. Movement of virus to the site of replication within the host cell and release of the viral genome from the remainder of the virus



4. Viral replication within the host cell



5. Viral assembly and maturation



6. Viral release from the host cell.  

Methods

Macromedia Flash Professional 8 was used in constructing this animation.  Illustrations were drawn using Adobe Illustrator 10.0.3 and imported into Flash 8.

Discussion

1. Viral attachment or adsorption to the host cell  

A. Adsorption of an enveloped virus
 
In the first frame the virus is coming into contact with the cell and binding to cellular receptor proteins on the cell's surface.  These proteins are normal cellular proteins that the virus uses as the binding site to enter the cell.  Every virus uses a specific set of cellular receptor proteins it can bind, and this choice of receptor proteins plays a large role in determining which cells and tissues a virus can infect.  

B. Adsorption of a naked virus  

In the first frame the virus is coming into contact with the cell and binding to cellular receptor proteins on the cell's surface.  These proteins are normal cellular proteins that the virus uses as the binding site to enter the cell.  Every virus uses a specific set of cellular receptor proteins it can bind, and this choice of receptor proteins plays a large role in determining which cells and tissues a virus can infect.  

2. Viral entry into a cell  

A. Enveloped viruses entering by fusion  

In the first frame the virus is bound to its cellular receptor, and then the membrane of the viral envelope fuses with the cell's plasma membrane releasing the nucleocapsid into the cytoplasm of the cell.  

B. Enveloped viruses entering by endocytosis  

In the first frame the virus is bound to its cellular receptor, and then the plasma membrane of the cell engulfs the virus with its envelope into an endocytic vesicle that travels into the cytoplasm of the cell.  

C. Naked viruses entering by capsid rearrangement  

In the first frame the virus is bound to its cellular receptor, and then the capsid proteins of the virus interact with the plasma membrane in a poorly understood mechanism releasing the viral nucleic acids into the cytoplasm of the cell.  

D. Naked viruses entering by endocytosis  

In the first frame the virus is bound to its cellular receptor, and then the plasma membrane of the cell engulfs the virus into an endocytic vesicle that travels into the cytoplasm of the cell.  

3. Movement of virus to the site of replication within the host cell and release of the viral genome from the remainder of the virus  

Viruses reproduce in specific locations within a cell.  In general RNA viruses reproduce in the cytoplasm of cells and DNA viruses move to the nucleus to reproduce because they need cellular DNA reproduction components found in the nucleus.  However some very large DNA viruses, such as the Pox viruses, produce the DNA replication components themselves and do not move to the nucleus.  

A. Release of virus from endocytic vesicle  

i. Fusion of envelope with endocytic vesicle  

In the first frame, the virus is moving within the cell to its preferred site of replication.  Once it reaches that site the viral envelope will fuse with the membrane of the endocytic vesicle, as is shown in frame 2.  This releases the viral capsid, containing the viral genome, into the cell's cytoplasm.  

ii. Lysis of endocytic vesicle  

In the first frame, the virus is moving within the cell to its preferred site of replication.  Once it reaches that site the virus will degrade the membrane of the endocytic vesicle, as is shown in frame 2.  This releases the viral capsid, containing the viral genome, into the cell's cytoplasm.  

iii. Capsid-endocytic vesicle interaction  

In the first frame, the virus is moving within the cell to its preferred site of replication.  Once it reaches that site, the virus capsid protein binds to the membrane of the endocytic vesicle and undergoes a conformational change by a poorly understood mechanism forming pores in the endocytic membrane.  This releases the genome into the cell's cytoplasm as is shown in frame 2.    

B. Site of RNA virus replication  

In the first frame the viral nucleic acids are still contained by the viral capsid proteins.  As most RNA viruses reproduce in the cell's cytoplasm, the virus will uncoat and reproduce within the cell's cytoplasm as shown in frame 2.  

C. Site of DNA virus replication  

i. Viral DNA genome entering the nucleus  

DNA viruses usually replicate in the nucleus of the cell which requires them to move into the nucleus.  In the first frame, an uncoated viral genome (that has been released from the viral capsid) moves from the cytoplasm of the cell through a pore in the nuclear membrane into the nucleus.  

ii. Capsid-nuclear pore interaction  

DNA viruses usually replicate in the nucleus of the cell which requires them to move into the nucleus.  In the first frame, a viral genome that is still surrounded by viral capsid proteins moves through the cytoplasm of the cell.  The capsid proteins interact with a pore in the nuclear membrane causing a conformational change in the capsid proteins that release the genome into the pore and allows it to enter the nucleus.  

iii. Nucleosome entering the nucleus  

DNA viruses usually replicate in the nucleus of the cell which requires them to move into the nucleus.  In the first frame, a viral genome that is still surrounded by viral capsid proteins moves through the cytoplasm of the cell and the viral nucleocapsid (capsid proteins and genome) pass through a pore in the nuclear membrane.  Once inside the nucleus, the viral capsid proteins are removed releasing the genome into the nucleus.  This mechanism is only used by very small DNA viruses, as most viral capsids are too large to fit through the nuclear pores.  

4. Viral replication within the host cell

A. Illustration of viral genomes, how they are replicated, and how they are transcribed into viral mRNA  

i. Double-stranded DNA  

To replicate the viral genome, DNA-dependent DNA polymerase enzymes (usually provided by the cell) copy both the positive and negative DNA strands producing double-stranded DNA viral genomes. To produce viral mRNA molecules, host cell DNA-dependent RNA polymerase enzymes copy the negative DNA strand into positive viral mRNA. The positive viral mRNA can then be translated into viral proteins by host cell ribosomes. Examples include most bacteriophages, Papovaviruses, Adenoviruses, and Herpesviruses.  

ii. Positive single-stranded DNA  

To replicate the viral genome, DNA-dependent DNA polymerase enzymes (usually provided by the cell) copy the positive DNA strand of the genome producing a double-stranded DNA intermediate. DNA-dependent DNA polymerase enzymes (again, usually provided by the cell) then copy the negative DNA strand into single-stranded positive DNA genomes. To produce viral mRNA molecules, host cell DNA-dependent RNA polymerase enzymes copy the negative DNA strand into positive viral mRNA. The positive viral mRNA can then be translated into viral proteins by host cell ribosomes. Examples include phage M13 and Parvoviruses.  

iii. Double-stranded RNA

To replicate the viral genome, viral RNA-dependent RNA polymerase enzymes (replicase) copy both the positive RNA and negative RNA strands of the genome producing double-stranded RNA genomes. To produce viral mRNA molecules, viral RNA-dependent RNA polymerase enzymes (transcriptase) copy the negative RNA strand into positive viral mRNA. The positive viral mRNA can then be translated into viral proteins by host cell ribosomes. Reoviruses are an example.    

iv. Negative single-stranded RNA  

To replicate the viral genome, viral RNA-dependent RNA polymerase enzymes (transcriptase) copy the negative RNA genome producing single-stranded positive RNA. Transcriptase must be carried into the cell with the virion.  Viral RNA-dependent RNA polymerase enzymes (replicase) then copy the positive RNA strands producing a single-stranded negative RNA viral genome. The positive mRNA strands also function as viral mRNA and can then be translated into viral proteins by host cell ribosomes. Examples include Orthomyxoviruses, Paramyxoviruses, and Rhabdoviruses.  

v. Positive single-stranded RNA

To replicate the viral genome, viral RNA-dependent RNA polymerase enzymes (replicase) copy the positive RNA genome producing single-stranded negative RNA. Viral RNA-dependent RNA polymerase enzymes (replicase) then copy the negative RNA strands producing a single-stranded positive RNA viral genome. To produce viral mRNA molecules, RNA-dependent RNA polymerase enzymes (replicase) copy the negative RNA strand into positive viral mRNA. The positive viral mRNA can then be translated into viral proteins by host cell ribosomes. Examples include Picornaviruses, Togaviruses, and Coronaviruses.    

vi. Positive single-stranded RNA retroviruses

To replicate the viral genome, viral reverse transcriptase enzymes (RNA-dependent DNA polymerases) copy the positive RNA genome producing single-stranded negative DNA strands. Viral reverse transcriptase can also function as a DNA-dependent DNA polymerase enzyme and will copy the negative DNA strands to produce a double-stranded DNA intermediate. Reverse transcriptase must be carried into the cell with the virion.  The viral DNA will move to the nucleus where it integrates into the cell's DNA using the viral enzyme integrase which also must be carried into the host cell with the virion.  Once in the host cell's DNA, host cell DNA-dependent RNA polymerase enzymes then copy the double-stranded DNA strands to produce single-stranded positive RNA genomes. To produce viral mRNA molecules, host cell DNA-dependent RNA polymerase enzymes copy the double-stranded DNA strand into positive viral mRNA. The positive viral mRNA can then be translated into viral proteins by host cell ribosomes. Retroviruses, such as human immunodeficiency virus type 1, human immunodeficiency virus type 2, and human T-cell leukemia virus type 1 are examples .

B. Viral replication  

Viruses will begin an infection by adsorbing to a cell, entering, uncoating, and releasing the genome.  The first frame shows an uncoated viral genome replicating by complementary base pairing.  The viral genomes are then transcribed into viral mRNA molecules by complementary base pairing in frame 2. In frame 3, the viral mRNAs are translated into viral proteins by host cell ribosomes.  

5. Viral assembly and maturation  

A. Enveloped viruses released by budding  

During maturation the viral capsids assemble spontaneously around the viral genomes.  In enveloped viruses that will leave the cell by budding, viral-encoded envelope glycoproteins are incorporated into the host cell membranes by the Golgi apparatus.  Frame 1 shows viral envelope proteins accumulated in the cell's plasma membrane while the viral genomes are surrounded by capsid proteins.    

B. Enveloped viruses released by exocytosis  

During maturation the viral capsids assemble spontaneously around the viral genomes.  In enveloped viruses that will leave the cell by exocytosis, viral-encoded envelope glycoproteins are incorporated into the host cell endoplasmic reticulum or Golgi apparatus membranes by the Golgi apparatus.  Frame 1 shows viral envelope proteins accumulated in the cell's endoplasmic reticulum membrane, while the viral genomes are surrounded by capsid proteins and then bud into the lumen of the endoplasmic reticulum .    

C. Naked viruses  

During maturation the viral capsids assemble spontaneously around the viral genomes as is shown in frame 1.    

6. Viral release from the host cell

A. Enveloped viruses released by budding  

During maturation the viral capsids assemble spontaneously around the viral genomes.  In enveloped viruses that will leave the cell by budding, viral-encoded envelope glycoproteins are incorporated into the host cell membranes by the Golgi apparatus.  Frame 1 shows viral envelope proteins that have accumulated in the cell's plasma membrane and a viral genome surrounded by capsid proteins leaving the cell by budding, pushing on the cell membrane that contains viral envelope proteins until it leaves the cell, taking some cell membrane with it that will serve as the envelope.   

B. Enveloped viruses released by exocytosis  

During maturation the viral capsids assemble spontaneously around the viral genomes.  In enveloped viruses that will leave the cell by exocytosis, viral-encoded envelope glycoproteins are incorporated into the host cell endoplasmic reticulum or Golgi apparatus membranes by the Golgi apparatus.  Frame 1 shows an enveloped virus in an excocytic vesicle, note the envelope was obtained by budding from either the endoplasmic reticulum or Golgi apparatus membrane, and shows the virus leaving the cell when the membrane of the exocytic vesicle fuses with the plasma membrane of the cell.    

C. Naked viruses released by host cell lysis  

Once large numbers of viral genomes are surrounded by viral capsid proteins, naked viruses leave the cell by degrading the cell membranes causing cell lysis, as is shown in frame 1.  

7. Summary of viral life cycles

A. Enveloped viruses  

This animation will take you through the entire life cycle of an enveloped virus.  It begins with adsorption in frame 1, when an enveloped virus binds to cellular receptor proteins on the host cell's plasma membrane.  In frame 2, the viral nucleocapsid will enter the cell by fusing its envelope membrane with the plasma membrane of the cell.  Note that enveloped viruses can also enter the cell by endocytosis in the same mechanism as a naked virus.  In frame 3, the viral genome will be released from the nucleocapsid, this can occur in either the cytoplasm, as with most RNA viruses, or in the nucleus as with most DNA viruses.  In frame 4, the virus genome reproduces by complementary base pairing, and then in frames 5 and 6 produces viral mRNA and directs the host cell's translation machinery to produce viral proteins.  In frame 7, viral envelope glycoproteins accumulate in the host cell plasma membrane, Golgi apparatus, or endoplasmic reticulum membranes as the viral genome is surrounded by viral capsid proteins.  In frame 8, the virus leaves the cell via budding from the plasma membrane.  Note the virus can also bud out of the endoplasmic reticulum or Golgi apparatus and then be packaged in an excocytic vesicle and leave the virus by exocytosis.  

B. Naked viruses  

This animation will take you through the entire life cycle of a naked virus.  It begins with adsorption in frame 1, when a virus binds to cellular receptor proteins on the host cell's plasma membrane.  In frame 2, the viral nucleocapsid will enter the cell by being engulfed in an endocytic vesicle.  In frame 3, the endocytic vesicle moves with the host cell to the preferred site of viral replication.  In frame 4, the virus leaves the endocytic vesicle by degrading the membrane.  Note: the virus can also leave by an interaction between the capsid proteins and the endosome's membrane-forming pores.  In frame 5, the viral genome is released from the nucleocapsid, this can occur in either the cytoplasm, as with most RNA viruses, or in the nucleus as with most DNA viruses.  In frame 6, the virus genome reproduces by complementary base pairing, and then in frames 7 and 8 produces viral mRNA and directs the host cell's translation machinery to produce viral proteins.  Once a great deal of viral genome and capsid proteins accumulate, the virus begins to be packaged into capsids spontaneously as shown in frame 9.  Once large numbers of virus are produced, the cell is lysed and the virus is released as shown in frame 10.  

References

1.  Flint, S. J., L. W. Enquist, R. M. Krug, V. R. Racaniello, A. M. Skalka.  2000.  Principles of virology, molecular biology, path ogenesis, and control.  ASM Press, Washington, DC.

2. Strauss, J. H., and E. G. Strauss.  2002.  Viruses and human disease.  Academic Press, San Diego, CA.

3.  Wagner, E. K., and J. Martinez.  2004.  Hewlett basic virology, 2nd ed.  Blackwell Publishing, Malden, MA.

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