Influenza virus are a family of RNA viruses that causes infectious diseasecalled influenza or commonly known as flu which infects the respiratory system.Influenza is very contagious and normally spreads when the infected personcoughs or sneezes. A person can also catch flu if a person comes in contactwith the infected person. When exposedto virus, person starts to show symptoms only after few days and lasts for 6-8days.
In some other case, it may last up to 2 weeks. So it is possible, aperson may not be aware that the individual themself may be affected and mightaffect other people without even the symptoms showing up. Symptoms and signscan be fever, sore throat, headache, nasal discharge, weakness and severe fatigue,loss of appetite, muscle and body aches and many more. Most people recover within weeks but it canlead to death especially people with high risk. Infants, young children andsenior adults are considered high risk. According to University of MarylandMedical center 35,000 people die every year in United states because of flu.
REF There are four types of influenza viruses.They are type A, type B, type C and type D. They all are identified by antigenic differences in their nucleoproteinand matrix protein. The influenza virus A and B are also known as Humaninfluenza because they frequently spread in people are the cause of seasonalepidemics almost every winter. Influenza virus A is the one that causesworldwide epidemics. Influenza virus A are classified into subtypes accordingto their combination of the hemagglutinin and the neuraminidase (NA) which are the proteins on the surface. There are 18 different types of hemagglutinsubtypes and 11 different types of neuraminidase subtypes. Currently A(H1N1)and A(H3N2) are circulating in human.
Influenza virus B are not divided into subtypes but are broken down tolineages and currently B/Yamagata or B/ Victoria lineage is circulating. Influenzatype C causes mild respiratory problems and are not considered epidemics. They are detected less frequently.
They caninfect human, pigs and dogs. Influenza type D does not affect or cause illnessto people, they primarily only affects cattle. Influenza virus changes constantly and theycan change in two different ways. One way is antigenic drift and the other wayis antigenic shift. Antigenic drift is when small changes are made in the genesof influenza, which happens continually over time as the virus replicates. Whenthese small genetic changes occur, they produce viruses that are closelyrelated to each other. When the virus replicate, the daughter virus is slightlydifferent and overtime the small changes will be different enough to allow evadingantibodies making the person is immune to previous strain fall ill. When newtype of virus are produced but are closely related, they share the sameantigenic properties and immune system which have previously responded to thattype will usually recognize and respond, and this is sometime calledcross-protection.
These small genetic changes won’t makedifference but overtime when the changes accumulates, it results in virus thatare antigenically different which immune system may not recognize the virus andthe person will fall ill again. If there is no vaccine for that type of virus,it could be epidemic. Virus are constantly evolving, that is why flu vaccinecomposition is reviewed each year.
If the other change was antigenic drift,the other type of change is antigenic shift where there is a major change directlywithout accumulation. Major geneticchange results in new hemagglutunin or both new hemagglutinin and neuraminidaseproteins which results in new influenza A subtype virus which the immune systemwont recognize and the people won’t have any immunity causing it to quicklyspread and causing pandemic. One exampleof recent shift occurred in the spring of 2009, when A(H1N1) virus which wascirculating prior 2009 was replaced byA(H1N1)pdm09 which emerged with new combination. The entire viruses are named usingdifferent components. They are named by combining antigenic type, whether A,BOR C, the host of origin, location of it where it was first identified, strainnumber, year or origin and subtype which are the different hemagglutinin andneuraminidase. Antigenic drift happens all the time whereas antigenic shifthappens occasionally. Antigenic drift and antigenic shift happens due tomutation during replication because RNA polymerase complex doesn’t have proofreading activity therefore higher mutation rate.
Higher mutation rate gives thevirus advantage against the existing immunity. Type A mutates most of the time whereasType B doesn’t mutate as often. The hemasgglutinin causes infection by bindingto the host’s receptors as with contact or other respiratory secretions from aninfected person. Antigenic shift can also occur when there is a viruscirculating around animal and suddenly the mutation in the virus allows them toinfect the human. If an animal is infected by a human virus and at the same isalso infected by animal virus, the genome might reassort and allowing the newvirus to have a mix RNA segment with completely new hemagglutunin andneuraminidase. The new virus will infect and spread rapidly. One of the majorinfluenza pandemics was Spanish flu in 1918, which killed 3% of the worldpopulation.
There are many types of influenza virus butonly Type A, Type B and Type C infect human. Each has slightly different genomeand proteins. Influenza virus belongs to family orthomyxoviridae. Type A andType B have genome made of 8 RNA segments and Type C has 7 RNA segments genome,which contains few genes. Type A is the most common type of influenza virus andas we know it is divided into further subtypes based on two glycoproteins,which are based on its protective envelope surface.
Type b has fewglycoproteins than Type A, thus doesn’t mutate frequently because they have fewglycoproteins, which doesn’t change as much as Type A. Type C useshemegluttinin esterase-fusion protein instead of just hemagglutin orneuraminidase to enter and exit cells. When the flu virus enters the body, it useshemagglutinin to bind to sialic acid sugar on the surface of epithelial cell inthe upper respiratory tract. Sialicacids are nine carbon acidic monosaccharides which are commonly found at thetermini of many glycoconjugates . Sialicacid form a-2,3- or a2,6- linkage which is recognized by the hemagluttininspikes. Confromational changes in hemagluttinin occur due to low pH, resultingin exposure of fusion peptide that merges the viral envelope and the endosomalmembrance.
Merging causes the pores to open releasing viral RNP’s into thecytoplasm of the host. After theprocess, hydrogen ions are pumped into the virus particle from endosome via M2ion channel. This causes internal acidification of the virus which interruptsthe interaction between protein in virus and ends up releasing viral RNP’S intothe cellular cytoplasm.
This process can be called endocytosis. Once the viral RNP’s are inside, they aretrafficked to the nucleus by nuclear localization signals. These nuclearlocalization signals, which are viral proteins, directs cellular proteins tomove the RNP’s and any other viral proteins towards and into the host cellnucleus. Nucleus serves as the location for the influenza virus RNA synthesiswhere host mRNA is used as the template for cell translation of viral proteinsand vRNA segments. With other protein viral RNA-dependent RNA polymerase, whichis also imported into the nucleus uses negativesense vRNA as a template toproduce two RNA species which are positive sense. RNA- dependent RNA polymerasealso produces mRNA templates, which is used for viral protein synthesis, and cRNA,which stands for complementary RNA.
cRNA is essential for RNA polymerase totranscribe further copies of negative-sense vRNA. But the viral mRNA is not like the hostcell mRNA, where the host cell mRNA is polyadenylated by specific poly(A)polymerase. For the viral mRNA to be exported and translated it needs to bepolyadenylated and capped inorder to function like host mRNA. Influenza virusmRNA has codes for negative-sense vRNA of 5 to 7 uracil residues which is transcribedinto positive senses by viral polymerase into a string of adenosine that formspoly(A) tail. Next step, a process called cap snatching occurs which caps themRNA with the help of PB1 and PB2 proteins from the host pre-mRNA. It stealsthe 5′ capped primer from host pre-mRNA trancripts and starts to synthesisviral mRNA like host mRNA. Viral protein called M1 and NEP/NS2 exports vRNAsegments. Interaction between M1 and both vRNA and NP occurs to being both ofthem together close to RNP complex.
Production of viral proteins begins onmembrane bound ribosome into endoplasmic reticulum. As the production of viralproteins beings, they are transported to golgi apparatus for translationalmodification. The envelope of viral proteins will contains hemagglutunin,neuraminidase and M2 which are all sorted by sorting signals to the cellmembrane for assembly. Once the viral proteins are assembled and packaged theyneed leave the cell to infect other cells and influenza virus leaves the cellby budding out.
Budding out is triggeredby the accumulation of M1 matrix protein in the cytoplasm. Viruses are releasedby NA protein activity, which anchors to the viral envelope by transmemerncedomain. If the NA are absent or not functioning properly, the affect of virusis reduced. NA also prevents viral aggregation by removing sialic acid residuesfrom the virus envelope, which enhances infecivity. It is also breaks downmucins in respiratory tract secretion, which allows penetration by virus to therespiratory epithelium. Streptococcus pneumonia is a gram positive and alpha-hemolytic bacterium. It belongs to themember of genus streptocococcus. They are lancet shaped and facultativeanaerobic bacteria.
There are known to be more than 90 strain of S.pneumoniaewhich most of them all causes diseases. There have been extensively studiedsince its isolation in 1881. They growin pairs or short chains but can also grow as single cell and they have a threemajor surface layers which are easily distinguishable in their surface. Cell wall, plasma membrane and capsule. Cellwall contains triple layered peptidoglycan backbone and the capsule is thethickest. Capsule is made up of repeating oligosaccharides units which can havefrom two to eight monosaccharaides. Itgrows best in 5% carbon dioxide and requires catalase to grow on agar plate.
S.pneumoniae causes more death than more od the other infectious disease andthe highest risk are the small children and elderly because they have weakerimmune. Pneumococcal infection can spread fromperson to person via droplet or aerols and colonizes nasopharyngeal. Pneumococcalenter via nasal cavity and attaches to the nasopharyngeal epithelial cells. Itcan stay there or spread to other parts of the body.
The intial step ofpneumococcal infection is when it attaches to the nasopharynx. Depending on thehost’s defence, virulence of the organism, preceding infection it can spread tolungs.