Gene Expression in viruses



Gene Expression in Viruses:

 Virus  ( venom or poisonous fluid) is a  nucleoprotein entity, which ' lives'as   intracellular obligate parasite it is able to utilise the synthetic machinery of host cell for its multiplication without involving growth and division. It is insert in cell free environment. An intact virus lying outside the host cell is called virion. Virus becomes active only when it enters a living cell.


☆ Virid: In 1971, T.O. Diener discovered a new infectious agent that was smaller than  viruses and caused potato spindle tuber disease. Smallest known agent of infectious disease. Known only from plants, they comprise single stranded low weight molecules of  RNA but lacking proteinaceous capsids. Found almost exclusively in nucleus of infected cells.



☆ Prion : An infectious  proteins devoid of  nucleic acid .It is malformed version of a normal cellular   protein which apparently replicates by recruiting normal proteins to adopt its form, being capable of infecting other cells of the same or a different  organism. Prions are thought  to cause certain degenerative diseases of nervous system e.g., Creutzfeldt_ Jacob disease ( CJD) and Gerstmann Straussler syndrome in humans.


☆ Virusolds ( also called  satellite  RNAs): These are small RNAs found in plants. These are encapsidated by plant viruses  and packaged together with a viral genome. Virusoids cannot replicate independently,  and do soon with the help  of an associated  virus. Such genetic  RNA  contains information which is normally  found in  DNA  in higher organisms. 

The first virus to be  discovered  was tobacco mosaic virus though vaccine  against  viral diseases  has been developed earlier ( antismall pox, Jenner 1796, antirabies, Pasteur 1880). Tabacco mosaic virus causes stunted growth and mottled leaves in Tabacco. Adolf Mayer discovered  that  tobacco  Mosaic disease could be transferred  from diseased  plant to healthy one through the sap of infected plant. 
D.J  Ivanowsky recognized certain microbes as causal organism of the mosaic disease of tobacco. These were found to be smaller than bacteria because  they passed through bacteria_ proof filters. M.W. Beijerinek demonstrated that the extract of the infected plants of tobacco could cause infection  in healthy  plants and called the fluid as Contagium vivum fluidum, i.e., infectious living fluid. The term virus was coined by Pasteur. Stanley was  the first to isolate tobacco Mosaic virus and crystallise the same. He showed crystals consist largely of proteins. He also observed  plant virus for the first time under electron microscope. Pollo virus was the first to be cultured over live medium by Enders. Hershey and Chase confirmed that  DNA is  genetic  material in bacteriophages. Retroviruses were discovered  by Temin ( 1970).

Nature: Viruses  do not have  cellular  structure.  They cannot be placed amongst  living beings, because outside the living cells they are  just  like nonliving chemicals which can be crystallised and stored indefinitely. A biosynthetic machinery is absent. There is no system to liberate energy. Viruses do not grow, divide or reproduce like typical organisms.  Instead, they multiply inside living cells by using host machinery,i.e., enzymes,  ribosomes,  nucleotides ,etc. They are, therefore, called living chemicals or nucleoprotein entities. 


Size: Viruses   are the smallest  entities. The smallest  virus is Foot and Mouth Virus with a size of 10 nm. The smallest  plant virus Alfalfa Mosaic. Virus with a diameter  of only 17 nm. The largest virus is Beetle Yellow ( 1250 × 40 nm), Pseudomonas Pf and Salmonella IF2 ( 1300 × 6nm). Tabacco Mosaic virus has a length  of 300 nm and a diameter  of 17.5 nm. 


Shape: Viruses have three  basic types of shapes__ helical , caboidal and binal. Helical viruses  have an elongate body ( e.g., Tabacco Mosaic Virus or TMV). Cuboidal viruses have short and broad body which may be rhombic, rounded or polyhedral (e.g., Influenza, Mumps, Herpes viruses). Binal viruses  possess a polyhedral head and helical tail ( e.g., T4 bacteriophage).

Types of gene expression in Viruses:

Types:Viruses  are host specific.  Holmes has divided viruses into three groups:

(a) Plant  Viruses ( Phytophagineae). They causes disease in plants, e.g., Tabacco Mosaic  Virus); Potato Mosaic Viruses,  Banana Bunchy Top Virus. Tomato Leaf Curl Virus. Majority of plant viruses  have single stranded RNA as genetic material but many possess DNA ( e.g., Cauliflower Mosaic Virus). In plant the symptoms of viral infection can be Mosaic formation,  leaf rolling  and curling,  yellowing  and vein clearing,  dwarfing and stunted growth.


(b) Animal Viruses (Zoo_ phagineae). They parasitise animals including human beings, e.g., Polio_ myelitis Virus, Influenza Virus, Small Pox Virus, Hepatitis Virus, Herpes virus, Mumps Virus, Rhino Voruses ( common cold viruses). In general viruses that infect animals have either single or double stranded RNA or double stranded DNA. 

(c) Phagineae: They  parasitise lower organisms:_ bacteriophages ( bacterial viruses, e.g., T2,T4, lambda), coliphages ( bacteriophages of Escherichia coli), cyanophages ( blue__ green algal viruses,  e.g., LPP_1, SM_ 1,N_1), phycophages ( algal viruses),mycophages ( fungal virus), zymophages ( mycophages of yeast),  Bacteriophages are usually double stranded DNA viruses. 



Components of Viruses:

A virus consist of two parts : 

1):   Nucleoid ( genom)

2): Capsid

An envelope is present in some cases. A few enzymes  are also known. 

1): Nucleoid:

It represents the virai chromosome. It is made of a single molecule of  Nucleoid acid. It may be linear or  circular . Nucleoid is the infective part of virus.It is coiled by means of polyamines. The nucleic acid is either DNA or RNA but never both. DNA  containing  viruses  are called deoxyviruses while RNA_ containing viruses  are termed as riboviruses. Each of them has two subtypes, double stranded and single stranded.


(i) Double stranded or dsDNA : It occurs in T2, T4, bacteriophages,  coliphage Lambda, Cauliflower Mosaic, Pox Virus,Adenovirus,  Herpes Virus ( linear), Polyoma Virus, Simian Virus__ 40 ( SM40), Hepatitis B ( circular).


(ii) Single Stranded or ssDNA: Coliphage MS 2, fd ( linear), Coliphage ΓΈ× 174 ( cricular).The single strand of DNA is called plus strand. A complementary or negative  strand DNA is synthesised to produce DNA duplex for replication  during multiplication of virus.


(iii) Double Stranded or dsRNA: It is found in Reovirus and Tumour Virus ( both linear).


(vi) Single Stranded or ssRNA: The condition is more common in riboviruses. The single strand RNA is generally linear, e.g., Poliomyelitis Virus,  Foot and Mouth disease Virus, Influenza Virus, Tobacco Mosaic Virus ( TMV), Tobacco  Necrosis Virus, Potato Mosaic virus, Bean Mosaic Virus, Retroviruses. Retroviruses have two copies of single stranded RNA ( hence diploid), e.g., HIV ( Human Immunodeficiency Virus,  HTLV_ III, AIDS Virus, l), HTLV_ I, HTLV_ II ( Human T_ lymphotrophic Viruses), Rous Sarcoma Virus ( RSV of Mouse). In some riboviruses, the RNA can directly  function as template and take part in replication ( e.g., TMV, Influenza Virus,  Paramyxo virus). In other riboviruses the RNA of the  nucleoid is first employed  in synthesising complementary DNA  through  reverse transcription ( e.g., Oncogenic Viruses,  HIV). Because  of the latter these viruses are called retroviruses. 

 The viral chromosome does not contain many genes.  T4 bacteriophage contains  about 100 genes. 


2): Capsid:

( Sheath, Coat ). It is the proteinaceous covering around the virus, which protects the nucleoid . The Capsid consists of subunits called capsomeres. The capsid of TMV has 2130  capsomeres. In binal bacteriophages the capsid sheath of tail is contractile. 


3): Envelope:

It is a loose membranous covering that occurs in some animal viruses,  rarely plant and bacterial  viruses. In contrast to enveloped viruses,  the viruses without an envelope are called naked. Envelope consists of proteins from ( virus),  lipids and  carbohydrates  (from host).It has subunits called peplomeres.Surface of envelope can be smooth or have outgrowths called spikes.Common enveloped viruses are HIV, Herpes  Virus, Vaccinia Virus, etc.


4): Enzymes :

They are occasional.  Enzymes  lysozyme is present  in the region that comes in contact with host cell in bacteriophage,  neuraminidase in Influenza Virus ,RNA polymerase,  RNA transcriptase, reverse transcriptase.

Reproduction:

It is of two main types , phagic and pinocytic. Phagic reproduction is of further two types, Lytic and Lysogenic.

1): Lytic Cycle:

It is the reproductive cycle of virulent phages, e.g., T2 bacteriophage, T4 bacteriophage. The phage attaches itself to the host cell ( e.g., Escherichia coli) through its tail fibres. The tip of the tail produces a hole in the bacterial cell wall  by means of enzyme  lysozyme. The tail sheath contracts and injects the viral genome into host cell. After entering  the host cell, the viral DNA  transcribes some early mRNAs to form some enzymes over the host ribosomes. Some of these are nucleases. The degrade host DNA and mRNAs. Ribosomes and tRNAs remain unaffected. Phage DNA and mRNA are also protected  from nucleases due to methylation of their cytosine bases. Parent viral  DNA functions as a template and replicatedly with the help of bacterial nucleotides. 

 Simultaneously,  host machinery ( ribosomes, tRNAs ,  amino acids , energy) is used by phage genes  to synthesis proteins for viral   lysozyme,  internal  proteins and capsid  proteins .Different  components combine to form new viruses.  The host cell ruptures by means of lysozyme releasing the phage particles. The period between  entry of viral nucleoid into host cell and bursting of host cell to release  new viruses  is called eclipse period.

2): Lysogenic Cycle:

Lambda phage ( l phage) has a higher degree of regulation of its  genes.  The phage is parasitic  over Escherichia coli. It does not possess  tail fibers for attachment  to bacterial cell. The tail directly comes in contact with bacterial cell, drills a hole in the wall and injects the phage DNA into the cell.In lysogenic cycle the phage DNA does not take over the control of cellular machinery of the host. Instead, it produces  a repressor ( e.g., CI) and undergoes reduction  to temperate or nonvirulent state. With the help of  enzyme integrase the viral genome becomes integrated  with the chromosomal DNA of the bacterium at a specific site. ( e.g., galactose locus in l phage). In this form the viral genome is called prophage.Prophage replicates along with bacterial chromosome and, therefore, gets distributed to the daughter bacteria.  Prophage does not form virus particles  because  the  genes  connected with taking over of  host machinery  remain repressed due to formation  of a repressor. At times the synthesis  of repressor is stopped. Repressor can also be destroyed by chemicals, high__ energy  radiations like UV radiations  and other adverse conditions. This converts the temperate or nonvirulent virus into virulent or lytic virus. Therefore, the bacterial  cell carrying  prophage is called lysogenic cell and the phenomenon of existence of virus genome in prophage  stage alongwith host DNA is termed as lysogeny.The conversion of  prophage  into   lytic virus, results in lysis of the cell with release of new phage particles called phage lysates. These phage particles may carry some genes  of bacterial cell with them. These phages can get attached  to other bacterial  cell, which may be lysogenic or non_ lysogenic. In this way, these phages can introduce bacterial DNA into a new recipient bacterial cell. This transfer of DNA from one bacterium  to the other through the agency of a bacteriophage is called Transduction. Transduction can be generalized  or specialized ( restricted). In genralized transduction  all fragments  of bacterial  DNA have a chance to enter a transducing phage. In specialized  Transduction  temperate phage can transfer only a few restricted  genes  of bacterial chromosomes. Most specifically,  the phage transduces only those bacterial  genes, which are adjacent  to the prophage in the bacterial  chromosome. 


   Transduction  is said to be complete when phage DNA is attached  to bacterial  DNA, acts as prophage and passed on to next generations of bacteria  along with the bacterial chromosome. This sequence of events  is not observed  in abortive transduction, which is usually  seen in cases of generalized transduction. Actually in almost all cases of generalized  transduction,  very little or none of the phage DNA is carried  in the transducing  particle,  which consists  primarily  of donor DNA surrounded by a phage envelope. It results  in inability of the transducing particle to establish  a lysogenic relationship  with the host and to replicate along with it.Thus, this transducing DNA may remain in the cytoplasm as a free but non__ replicating  molecule. When this recipient bacterium  will divide, the transducing fragments  will be retained  by only one of the two daughter  cells. Thus only one daughter  cell in each generation  of bacterial  cells carries  the transducing  fragments  while all other cells are of the nontransduced phenotype..This is called abortive Transduction 

   Transduction  is usually  a byproduct  of the phage life cycle without an obvious  benefit for the phage. Transduction  has also been reported even in eukaryotes like men and mouse.


3): Single Stranded DNA phages:  

The phage ΓΈ × 174 has single stranded DNA..It is known as plus strand. Before multiplication, the plus strand DNA synthesises a complementary  ir negative  strand DNA to become double stranded or replicative.The replicative or double stranded DNA then  takes  over the cellular  machinery  of the host and forms a number of copies of phage or plus DNA over the negative  one.


4): Pinocytic Reproduction:

This mode of reproduction  is found in several  plant and animal viruses, e.g., TMV ( Tobacco Mosaic Virus), Herpes Virus, HIV,( AIDS  Virus), Hepatitis B Virus, etc. The virus  possesses  chemicals  which help both in attachment  and penetration.  The whole of virus particle enters the host cell except  the envelope  ( e.g., HIV) if present; inside the host cell, it separates into its components,  capsid elements  or capsomeres and viral genome or nucleoid. Replication of viral genome occurs  by two methods in RNA__ viruses. 


( a) RNA _ RNA Viruses: In some RNA  viruses ( e.g., TMV  , Influenza, Mumps, Measles) the viral  genome (RNA molecule) after entering  host cell produces an enzyme called replicase. With the help of replicase the RNA genome   synthesises more RNA genome  directly  without DNA formation. The RNA genome  also synnthesises mRNAs  for producing proteins  over the host ribosomes  with the help of  tRNAs  and amino acids of the host.



RNA πŸ”πŸ”RNA ➡️➡️mRNA ➡️Protein


(b) Retroviruses ( RNA_ DNA Viruses, Tumour or Cancer Viruses): In HIV ( Human Immuno_ deficiency Virus), tumour and oncogenic viruses ( Rous Sarcoma Virus), the RNA genome cannot directly  replicate after entering the host cell.The viruses  possess  an   enzyme called reverse transcriptase ( Temin and Baltimore, 1972). With the help of  this enzyme  the viral RNA first synthesises single stranded copy DNA ( cDNA) over it. RNA degenerates and the single stranded cDNA forms its complementary strand. Reverse  transcriptase has modified  central dogma in molecular biology ( DNA➡️RNA➡️Protein) to the following. 

               
        transcription       translation 
DNAπŸ”πŸ”πŸ”πŸ”πŸ”RNA➡️➡️➡️➡️➡️ Protein 
        reverse transcription 

Reverse  transcription is useful in vitro formation  of a cellular  gene from a purified  mRNA.

Double stranded copy DNA integrates with the host chromosome ( like the viral DNA with bacterial   chromosome in lysogenic  cycle). The integrated copy of DNA virus is called provirus. Provirus produces chemicals that bring about changes in  cellular  machinery.HIV induced chemicals destroy immune system of the body. Oncogenic viruses  produce chemicals that bring about uncontrolled growth and division of cells  by either direct effect on cellular  oncogenes or through  transposons. Some 20 viral genes  are known to trigger cancer. They are called viral oncogenes. Slightly   modified forms of these genes  occurr in human  beings.  They are often called proto_ oncogenes. Cellular genes , which are known to take part in producing cancer, are termed as cellular oncogenes. They are normally involved in producing growth factor. At times they are changed to activated   cellular  oncogenes due to their placement in an area  where they undergo rapid expression.  Transposons or jumping  genes  are also known to bring about conversion of proto_ oncogenes into active oncogenes. Hepatitis B__ virus, Epstein __ Barr Virus, Herpes   Virus   and Papilloma  Virus  are involved  in different  types of cancers. 

  Ultimately  the provirus dissociates from tbe  host  genome  and transcribes viral RNAs, some of which function as viral genome while others help synthesise viral proteins and reverse transcriptase. The different  constituents assemble to produce  new viral particles. They may come out of the host cell through  exocytosis or directly pass on to other host cells through protoplasmic connections. 









































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