Orthomyxo Viridae:

 

Influenza virus:

 

 

 

 

 

 

 

Epidemiology: http://www.ufrgs.br/

 

 

 

 

 

 

 

Virus with glycoproteins; http://www.departments.bucknell.edu/

 

influenza-virion3

 

The influenza virion (as the infectious particle is called) is roughly spherical. It is an enveloped virus – that is, the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. Inserted into the lipid membrane are ‘spikes’, which are proteins – actually glycoproteins, because they consist of protein linked to sugars – known as HA (hemagglutinin) and NA (neuraminidase).http://www.virology.ws/

 

Morphology:

 

 

 

 

Another membrane protein found is Neuraminidase (NA).  This hydrolyses the link between terminal Sialic acid groups from Galactose or Galactosamine residues.  Breakdown of this link, at the time of infection, facilitates transport of viruses into cells through mucins.  About ~100 copies of this protein per virus are present on the viral membranes.

 

 

This colorized negative-stained transmission electron micrograph (TEM) depicts the ultrastructural details of a number of influenza virus particles, or “virions." Image: CDC/ Dr. F. A. Murphy

Read more at
: http://phys.org/news176055264.html#jCpViral shape; http://phys.org/

 

 

 

The influenza virus having genes from different species

Swine flu:  http://www.mcb.uct.ac.za/

 

 

Viral receptor on host cell

 

 

 

 

 

 

 

 

 

Viral glycoproteins on the surface interact with host cell receptors and bind; http://employees.csbsju.edu/

 

A surface protein on the surface of the viral particle-

Hemagglutinin; http://blogs.unimelb.edu.au/

 

                                                                                                       

                                       

File:Neuraminidase Ribbon Diagram.jpg

Neuraminidase; http://home.cc.umanitoba.ca/

 

 

 

 

 

 

 

 

Certain modification of Hemagglutinin has caused disease in pandemic proportion during different time periods in different countries; most of them originated from China.

 

 

 

Enveloped viruses gain entry to cells by use of specific viral proteins that have membrane fusion - inducing properties. The first of these viruses for which the entry process was figured out in detail was influenza. Influenza virions (see EM pictures) bind to sialic acid (also known as N-acetyl neuraminic acid) on the cell surface and are endocytosed. The endocytic vesicles become acidified (pH drops from 7 to around 5), and at this pH, the hemaglutinin (HA) trimers in the influenza envelope undergo a structural transition. At some stage the HA monomer is cut into two polypeptides, HA1 and HA2. When the pH drops to 5, the amino terminal end of HA2 flips "upward" from an internal position to become exposed to the aqueous environment. This end of HA2 (called the "fusion peptide") is highly hydrophobic, and it interacts with the vesicle membrane and causes the viral envelope and the vesicle membrane to fuse. (See figure.) This fusion event dumps the viral core into the cell's cytoplasm. (See a figure by Paul Digard, Department of Pathology, University of Cambridge.) 

Flu viral endocytosis and endosomal membranes; http://www.lehigh.edu/

 

 

 

                        Viral RNPs: http://www.microbiologybytes.com/

 

 

 

 

 

(-) genetic RNA replication; http://www.slangenforum.com/;http://www.slangenforum.com/

 

Dr. Margaret Hunt; http://www.thailabonline.com/

 

influenza-rna-synthesis

 

 

The enzyme that reproduces influenza RNA is known as an RNA-dependent RNA polymerase. This enzyme, which consists of the viral proteins PA, PB1, and PB2, is present in every virus particle. The influenza viral RNA polymerase is a primer-dependent enzyme. The enzyme cannot copy the (-) strand RNA template without a small piece of RNA that aligns on the template RNA and provides a starting point for RNA synthesis. The primers for influenza viral mRNA synthesis are produced from the cell’s own collection of mRNA molecules. The influenza viral RNA polymerase actually cleaves cell mRNAs near their 5′-ends, generating the primers it requires for RNA synthesis. This process has been called cap snatching, because the primers are made from the 5′-ends of cell mRNAs, which have an unusual chemical structure called a ‘cap’ (box labeled ‘c’ in illustration). Cap-snatching is also a feature of mRNA synthesis of other viruses. http://www.virology.ws/

 

influenza_virus_rna

 

Within the influenza A virion are eight segments of viral RNA. These molecules carry the all the information needed to make new influenza virus particles. These eight RNAs are shown schematically as olive green lines at the top of the illustration. RNAs are chains of four different nucleotides, A, C, G, U. In the case of influenza virus, the eight RNAs are a total of about 14,000 nucleotides in length. The nucleotides make up the genetic code – it is read by the cell’s translation machinery in groups of three, with each triplet specifying an amino acid.  Vincent Racaniell; http://www.virology.ws/

 

 

 

 

                    Influenza Virus Life Cycle: Adam; http://nursingcrib.com/

 

 

Infection:

 

Entry of viruses is through cell receptor and viral HA binding.  Hydrolysis of the link between the Sialic acid and Glycans, leads to internalization of viral nucleo capsid leaving the membrane. The viral membrane and its proteins merge with the host cell membrane.

 

·         They are then transported to the nucleus, via transport proteins. In the nucleus, perhaps the nucleo-protienaceous threads unfold. 

 

·         Viral Proteins such as PB1, PB2, PA, NS1 and NS2, which are bound to genomic RNAs, play an important role in replication of the genome. 

 

·         To begin with, PB1 and PB2 complex bind to the cap region of host’s mRNA (newly made ones), and cut 12 –13 ntds down stream from the cap either at A or at G, because G or A can pair with U.  Then the Cap-leader sequence is transposed and laid on the 3’ end of the genomic RNA in such a way, G or A can be paired with 3’U of (-) genomic RNAs. The G or A provides priming 3’OH group. 

 

·         Proteins PB1, PB2 and PA in association with nonstructural proteins such as NS1 and NS2 act as Transcriptase complex which extends the primer into a complementary copy of (-) RNA into (+) RNA.  Immediately, these transcripts are added with poly- (A) tail at the 3’ end by host enzymes, how? The answer is not clear. Even the process of poly-Adenylation cannot be explained, for the 3’ end of the (+) RNA does not show any polyadenylation signal sequences.  It is expected that the host enzymes bring about poly-(A) addition. 

 

·         Synthesis of (+) RNAs can considered as transcription (?) for it produces translatable RNAs.

 

 

A List of Influenza Genomic RNAs, Theirs Features:

 

Genomic-RNAs

Length in bases

Name of the

RNA

Function

 

1

2341

PB2

Produces-Transcriptase, cap binding

2

2341

PB1

Transcriptase, elongation

3

2233

PA

Transcriptase!

4

1778

HA

Hem-agglutinin, trimer, 135^Ao

5

1565

NP

Nucleoprotein,

6

1413

NA

Neuraminidase, tetramer, 60A^o

7.a

1027

M1

Matrix protein, major viral proteins

7.b

   “

M2

Ion channel, integral membrane protein

8.a

 

8.b

890

 

NS1

NS2

Nonstructural, nuclear

Nuclear and cytoplasmic

 

 

 

 

 

 

 

Influenza replication

http://www.microbiologybytes.com/virology/303

 

 

 

http://www.microbiologybytes.com/

 

 

 

Antigenic shift: It means that the gene coding for HA is totally replaced by another gene from another source i.e. replacement of HA of one species with another species from other source.  This can easily make human species not to recognize the earlier Flu infections.  By the time human immune system responds and raise and mount its immune attack; the damage to persons is considerable.  This is possible by mixed viral infection.

 

                                    http://employees.csbsju.edu/

 

Antigenic drift:  It means where the antigen gene has undergone point mutation. In a course of time it generates a different amino acid sequence in such a way, human immune system fails to recognize and attack.

 

http://employees.csbsju.edu/

 

Evidences suggest that before 1918, the major strain of influenza was H3N8.   This was replaced in the 1918 pandemic when an H1N1 virus arose.   In the next pandemic (Asian,1957)  three genes from avian influenza (PB1, HA, and NA) replaced their counterparts in the H1N1 strain, presumably through re-assortment as shown above, to give the pandemic strain H2N2.  Again through a similar process, the PB1 and HA genes from the prevalent strain where replaced by avian genes to produce the Hong Kong H3N2 pandemic strain.

In addition, the sequence of viruses can be compared and phylogenetic tree can be created, not unlike family trees of inheritance.  The 1918 virus appears most related to human and swine influenza virus, not avian, but it does clearly have avian features (such as the gene for HA described above).  It may have emerged from avian reservoir before 1918, for which no specimen has yet been found to compare.  That virus may have then acquired enough mutations to make it infective in mammals.  There is yet another possibility:  the 1918 virus came directly from a completely different avian source (somewhat like SARS which emerge from civets). http://employees.csbsju.edu/