Virus Life Cycle - The growth curve

The above image shows a Virus life cycle growth curve...

Now, let me explain more about it to give you a better understanding of this illustration!

The virus would first attach itself to the host and undergo it's replication cycle as explained earlier on in previous post, after which the virus would enter...

Eclispe/Latent stage

During this stage, there is a fall in virus titre as there are no infectious particles present in the infected host's bloodsteam while the virus is undergoing it's replication cycle.

Hence, the virus would not be detected by any external mediums whatsoever until it has been released.

Next, from the graph we can see a significant increase straight after the eclispe/latent stage.

This is known as the stage where the virus have burst, whereby new progeny virus has assembled and been released into the host's bloodsteam.

After being released into the person's bloodsteam, the body would begin to produce antibodies to fight the virus. After a certain period, the number of virus as can be seen from the illustration would begin to hold stable and soon after, decrease in numbers as the virus begins to die off.

After which, the infected host would recover completely and would be healthy once again!

Portals of entry

Virus can enter the body at several sites which are known as portals of entry.
There are four majoy portals of entry:

1) Skin
2) Mucuous membrane
3) Placenta
4) Parenteral route


Let's take a look at...

(1)Skin

The skin is a barrier to most pathogens if it is intact.
However, some pathogens can still enter via hair follicles, sweat glands and through cuts and bruises.

(2) Mucous membrane

There are mucous membrane linings in all of our body cavities such as...

1. Respiratory

2. Gastrointestinal
3. Urinary

4. Reproductive

5. Conjuctiva which is also known as our eyes.

Mucuous membrane, unlike our skin, are thin, moist and warm and it is also where all cells

are living.

(3) Placenta

Pathogens can also be passed from mother to fetus through the placenta. This would result in...

1. Spontanous abortion or otherwise better known as miscarriage

2. Birth defects

3. Premature births which may result in other complications

Lastly, we have...

(4) Parenteral route

This is the most common portal of entry route. Pathogens may infect host in this way via punctures, contaminated needles, bites, cuts, stab wounds or surgery.

Release

a. Naked viruses

Naked viruses are predominantly released by host cell lysis. While some viruses are cytolytic and lyse the host cell more or less directly, in many cases it is the body's immune defenses that lyse the infected cell.
For lytic viruses (most non-enveloped viruses), release is a simple process - the cell breaks open and releases the virus.

b. Enveloped viruses

With enveloped viruses, the host cell may or may not be lysed. The viruses obtain their envelopes from host cell membranes by budding. As mentioned above, prior to budding, viral proteins and glycoproteins are incorporated into the host cell's membranes. During budding the host cell membrane with incorporated viral proteins and glycoproteins evaginates and pinches off to form the viral envelope. Budding occurs either at the outer cytoplasmic membrane, the nuclear membrane, or at the membranes of the Golgi apparatus

Enveloped viruses acquire the lipid membrane as the virus buds out through the cell membrane. Virion envelope proteins are picked up during this process as the virus is extruded. Budding may or may not kill the cell, but is controlled by the virus - the physical interaction of the capsid proteins on the inner surface of the cell membrane forces the particle out through the membrane.

1. Viruses obtaining their envelope from the cytoplasmic membrane are released during the budding process

Release of an Enveloped Virus by Budding, step 1.

The virus obtains its envelope from the host cell's cytoplasmic membrane as it buds from the cell surface.

Release of an Enveloped Virus by Budding, step 2.

The virus obtains its envelope from the host cell's cytoplasmic membrane as it buds from the cell surface.


Transmission Electron Micrograph of Rubella Viruses Budding from a Host Cell

Image provided by Dr. Fred Murphy and Sylvia Whitfield.
Courtesy of the Centers for Disease Control and Prevention.
The rubella virus causes German measles. The virus gets its envelope by budding from the host cell's cytoplasmic membrane.

2. Viruses obtaining their envelopes from the membranes of the nucleus, the endoplasmic reticulum, or the Golgi apparatus are then released by exocytosis via transport vesicles.

Release of an Enveloped Virus by Fusion of a Transport Vesicle with the Host Cell's Cytoplasmic Membrane, step-1

The assembled virus is placed in a transport vesicle.


Release of an Enveloped Virus by Fusion of a Transport Vesicle with the Host Cell's Cytoplasmic Membrane, step-2.

The transport vesicle fuses with the host cell's cytoplasmic membrane releasing the vitrus from the cell.


Some viruses, capable of causing cell fusion, may be transported from one cell to adjacent cells without being released, that is, they are transmitted by cell-to-cell contact whereby an infected cell fuses with an uninfected cell.


The assembled virus is placed in a transport vesicle. Then, the transport vesicle fuses with the host cell's cytoplasmic membrane, releasing the virus from the cell.



The uninfected cells and infected cell then fuse together forming a multinucleated giant cell or syncytium.

Maturation

Maturation

The stage of the life-cycle at which the virus becomes infectious. Usually involves structural changes in the particle, often resulting from specific cleavage of capsid proteins to form the mature products, which frequently leads to a conformational change in the capsid, or the condensation of nucleoproteins with the genome. For some viruses, assembly and maturation are inseparable, whereas for others, maturation may occur after the virus particle has left the cell.

Generally, protein capsid is assembled around the viral genome

Fig. 1A: Maturation of an Enveloped Virus

Envelope glycoproteins are transported to the host cell's cytoplasmic membrane and the capsid assembles around the viral genome.



Fig. 1B: Maturation of a Naked Virus



The capsid assembles around the viral genome.

Replication & Expression

Alight, now that the uncoating is done, whaat's next? Replication!

What is replication?



Replication involves assembly of viral proteins and genetic materials produced in the host cell.


Replication of nucleic acid. Replication of viral nucleic acid is a complex and variable process. The specific process depends
on the nucleic acid type.



NOTE: Symmetrical transcription of DNA gives rise to double-stranded RNA.

DNA virus replication -with the exception of the poxviruses, all DNA viruses replicate in the nucleus. In some cases one of the DNA strands is transcribed (in others both strands of a small part of the DNA may be transcribed) (step 4) into specific mRNA, which in turn is translated (step 5) to synthesize virus-specific proteins such as tumor antigen and enzymes necessary for biosynthesis of virus DNA. This period encompasses the early virus functions. Host cell DNA synthesis is temporarily elevated and is then suppressed as the cell shifts over to the manufacture of viral DNA (step 6). As the viral DNA continues to be transcribed, late virus functions become apparent. Messenger RNA transcribed during the later phase of infection (step 6) migrates to the cytoplasm and is translated (step 7). Proteins for virus capsids are synthesized and are transported to the nucleus to be incorporated into the complete virion (step 8).

Assembly of the protein subunits around the viral DNA results in the formation of complete virions (step 9), which are released after cell lysis.
The single-stranded DNA viruses first form a double stranded DNA, utilizing a host DNA-dependent DNA polymerase. They then undergo a typical replication cycle.


RNA virus replication -with the exception of the orthomyxoviruses and retroviruses, all RNA viruses replicate in the cytoplasm of the host cell. The exact process varies with the species of virus. The single-stranded RNA that is released after uncoating will act as either: (a) the mRNA to synthesize viral-coded proteins; or (b) a template to synthesize mRNA; or (c) a template to synthesize double stranded RNA, which is then used as a template to synthesize mRNA; or (d) a template to synthesize double-stranded DNA, which is then utilized as a template to synthesize mRNA. This latter process occurs only with the retroviruses (oncornaviruses).
The replication of poliovirus, which contains a single-stranded RNA as its genome, provides a useful example. All of the steps are independent of host DNA and occur in the cell cytoplasm. Polioviruses absorb to cells at specific cell receptor sites (step 1) , losing in the process one virus polypeptide. The sites are specific for virus coat-cell interactions. After attachment, the virus particles are taken into the cell by viropexis (similar to pinocytosis) (step 2) , and the viral RNA is uncoated (step 3) . The single-stranded RNA then serves as its own messenger RNA. This messenger RNA is translated (step 4), resulting in the formation of an RNA-dependent RNA polymerase that catalyzes the production of a replication intermediate (RI), a partially double-stranded molecule consisting of a complete RNA strand and numerous partially completed strands (step 5). At the same time, inhibitors of cellular RNA and protein synthesis are produced. Synthesis of (+) and (-) strands of RNA occurs by similar mechanisms. The RI consists of one complete (-) strand and many small pieces of newly synthesized (+) strand RNA (step 6). The replicative form (RF) consists of two complete RNA strands, one (+) and one (-).

The single (+) strand RNA is made in large amounts and may perform any one of three functions: (a) serve as messenger RNA for synthesis of structural proteins; b) serve as template for continued RNA replication; or (c) become encapsulated, resulting in mature progeny virions. The synthesis of viral capsid proteins (step 7) is initiated at about the same time as RNA synthesis.

The entire poliovirus genome acts as its own mRNA, forming a polysome of approximately 350S, and is translated to form a single large polypeptide that is subsequently cleaved to produce the various viral capsid polypeptides. Thus, the poliovirus genome serves as a polycistronic messenger molecule. Poliovirus contains four polypeptides.

Click this website and take a look at the animations to get a better picture of about virus replication.

Http://biology.about.com/od/virology/a/aa11108a.htm

Uncoating

Uncoating : Uncoating occurs simultaneously with or rapidly after penetration. Hence, this stage is difficult to be studied and remains a relatively poorly understood stage of the replication cycle.

Uncoating in general refers

o the events that expose the viral genome to the host cellular machinery and sets the stage for the viral genome to express its functions required for the replication.

This stage occurs simultaneously with or rapidly after penetration. In order to express the viral genome to the cell organelles, it is necessary that the virion coat

e removed partially or completely. Therefore, once virions are in the cytoplasm, they are generally uncoated to some extent by a variety of processes, including simple dissociation and/or enzyme-mediated partial degradation of the particles, to release the viral geno

me as a naked nucleic acid or as a nucleoprotein complex.

The steps involved in the process of disintegration of the protein coat or capsid to release its genome into the cell is called as uncoating. Uncoating may be achieved by the complete or partial removal of the capsid.

Penetration

The next step in the virus replication cycle after the attachment is penetration. Penetration is the process by which the virus goes into the plasma membrane and prepare for is uncoating. Penetration of eukaryotic cells occurs in three ways.

The first way is the Receptor-mediated (enveloped-virus). It is a process by which cells internalize molecules by the inward budding cell membrane vesicles containing proteins with receptor sites specific to the molecules being internalize.

The virus binds to its specific receptor and goes into the plasma membrane.

The function of the receptor-mediated endocytosis is used for the specific uptake of certain substance required by cell.

Clathrin is another way for the penetration. Though both receptor mediated and clathrin are almost the same, clathrin usually occur for naked viruses whereas receptor mediated are for enveloped viruses.

The last one would be the fusion of enveloped virus. It is said to be a direct penetration method.

I'll end here for penetration. Enjoy!