Orthomyxoviridae Flashcards
Orthomyxoviridae genus
Influenza virus types: A, B, C; infect humans but can cycle through animal populations which may lead to genetic diversity which in turn can lead to antigenic variability A= Human, swine, avian, equine. B= human. C= human.
Orthymyxoviridae structure
- SS RNA, (-) polarity, 8 segments (A, B), 6 segments (C). The genome being negative polarity means that it is complementary to mRNA. Therefore, genomic stranded RNA must be converted to the + polarity form, the latter now serving as messenger.
- Helical nucleocapsid composed of RNA plus NP, PB1, PB2, PA
- 9 structural proteins: H (hemaggltinin), N (neuroamindase), PB1, PB1-F2, PB2, PA, M1 (matrix), M2 (matrix), NP (nucleocapsid protein), and 2 nonstructural (NS) (not part of the structure of the progeny virus)= 11 proteins total.
Several viral RNA segments encode for more than one protein.
- Envelope contains 2 glycoproteins, H (hemagglutinin), N (neuroaminidase)
- RNA dependent - RNA polyermase = PB1 (PB1-F2), PB2, PA, complex is part of the helical nucleocapsid
RNA-RNA polymerase (RNA transcriptase)
Negative stranded viruses have this protein. It is part of the nucleocapsid complex, which converts - RNA to + RNA, cells do not have a corresponding RNA polymerase primarily because the cell does not require RNA to RNA replication as part of their metabolism.
Influenza Virus Antigens
Nucleocapsid and M (matrix) proteins.
H ags; detected by hemagglutination, neutralization, C ixation
H and N are both strain specific AgS; eg. influenza type A, Hong Kong Strain.
Influenza Virus Replication Step 1 (attachment)
Attachment of virus particle to cell surface receptor. The hemagglutinins of the virus bind to sialic acid containing receptors.
The virus penetrates the cell by an endocytotic process and is enclosed within a vacuole. The acidic environment of the vacuole facilitates the hemagglutinin to initiate fusion between the virus envelop and the vacuole membrane. Acidicifaction of the virus core aids in the disassembly of the virus nucleocapsid thereby releasing the viral genome into the cytoplasm. The viral RNA along with the RNA polyermase complex and assessor proteins travels to the nucleus of the cell, which is the site of both transcription of viral mRNAs and viral genomic RNA.
Each genome RNA (-) is initially copied to (+) stranded which can act as either 1. mRNA or 2. as a template RNA involved in genome replication (viral RNA polyermase mediates both processes.)
Viral transcription/ Viral protein translation
Viral mRNAs are transcribed from negatiev stranded viral RNA templates in the nucleus. The viral transcripts are 20-30 nucleotides shorter than corresponding (-) stranded template RNA
The viral mRNAS have a 3’ poly A tail added and a donated short capped RNA at the 5’ end, (capped RNA primer is donated by cellular mRNA)
The process allows the - strand (that serves asd a template) to be copied into mRNA, thus one fo the requirements for nuclear involvement during influenza virus replication
each mRNA leaves the nucleus and moves to the cytoplasm; some viral mRNA (H and N mRNAS) are translated in association with the endoplasmic reticulum will other viral mRNAs are translated free in the cytoplasm.
The H and N glycoproteins then accumulate in the Golgi apparatus and are then inserted in the cell surface membrane where budding sites are formed.
Viral genome replication replication of RNA
Viral RNA polymerase (PB1) mediated viral genome replication occurs in nucleus
Negative stranded genomic RNAs are copied into full size + RNAs through the formation of a replicative intermediate (RI);
then the + RNA serves as a template for synthesis of many negative stranded RNAs (genomic RNAs that will end up in new progeny virus particles.)
newly synthesized viral genomic RNAs associate with newly synthesized nucleocapsid proteins and RNA polymerase proteins in the nucleus and are then transported out of the nucleus to the cytoplasm.
Viral genome replication 2 Budding and envelope
Nucleocapsid (8 segments( bds to acquire envelope; the process rquires that the nucleocapsid migrates to the budding sites that possess H and N viral proteins embedded in the cell membrane; after budding an extraellular virus is formed.
On the extracellular virus H protein present on Viral envelope is cleaved or uncleaved (HA1 +HA2)
Proteolytic cleavage of H = infectivity; ie virus prticle become infectious
N= neuroaminidase, important in budding of progeny virus particles (target for new antiviral drugs) and lowers viscosity of mucus in vivo during infections
W+ virus does not replicate well in TC, use embryonated egg, allantoic cavity for virus propagation.
Epidemic and pandemics: drifts and shifts Major antigen for immunity and antigenic drift
- major antigen for immunity = H, 11 H subtypes change in H affects antigenicity most, additive effect if N also changes
N antigenicity is also important, 8 N sybtypes
H and N varies antigenically due to point mutation (antigenic drift)
antigenic drift leads to epidmeics; existing ab in human population from previous infections by infleunza virus may not efficiently neutralize virus.
Epidemic and pandemics: drifts and shifts 2 antigenic Shift
H major antigenic variation due to reassortment between human and animal influenza virus “antigenic shift” responsible for pandemic which occur about every 10 years, exchange RNA segments between animal influenza virus and human influenza virus; N protein antigenicity can also be changed as a result of reassortment of the N gene.
as a result of shift, presentation of entirely new antigens to population with no immunity yields acute respiratory disease, no neutralization of virus by preexisting antibodies.
Epidemic and pandemics: drifts and shifts 3 Naming and antigenic sin
example designation for influenza A virus Type/Location of isolation/Date isolated (subtype)
Antigenic sin with each new infection with influenza A an individual responds with the strongest antibody against the 1st subtype, which infected that individual.
