Influenza virus

• There are three types of influenza viruses: A, B, and C. • Mostly infect human and birds (avian Influenza) • Humans can be infected with influenza types A, B, and C viruses• Most important serotypes are H1N1, H3N2

Structure• Enveloped ss – RNA virus• 6-9 nm dia. 600 nm long• Capsid is made up of matrix protein M1 • Several surface glycoproteins are present

• Hemagglutinin (HA): Trimers • Neuraminidase (NA): tetramers • M2 proteins

• RNA is segmented ; in Influenza A, it is 8 linear segments (890 2341 bases), Each is associated with a transcriptase complex• Nucleocapsid is helical, but virus is polymorphic (no

defined shape) due to the envelop• RNA depended RNA polymerases (convert – RNA to

+ RNA)• RNA endonucleases

• Life Cycle:• Attachment: Receptor is N-

acetylneuraminic acid• Penetration through endosomes • Replication:

• mRNA synthesis happens inside the host nucleus.

• Viral mRNA synthesis requires the activity of at least two influenza virus polymerase subunits, PB1 and PB2.

• Viral replication-transcription complex splice the host mRNA cap and use it as primer for viral mRNA. (Cap snatching or stealing)

• Using host splisosome the viral mRNA is spliced to 10 segments. Each segment now translate for a protein.

Influenza Antigenic shift and drift

• Antigenic shift refers to an abrupt, major change to produce a novel influenza A virus subtype in humans that was not currently circulating among people • Antigenic drift refers to small, gradual changes that occur through

point mutations in the two genes that produce hemagglutinin, and neuraminidase. • Antigenic drift produces new virus strains that may not be recognized

by antibodies to earlier influenza strains.

Pox virus

• DNA (ds) virus • Replicate in the cytoplasm and are independent of the host for

mRNA production• Large animal virus infect vertebrate and invertebrate • Mammal, Birds and insects

• Very large viruses (250–300 nm X 250 nm x 200 nm• Eg. Vaccinia (400 X 240 X 200 nm)

• Poxviruses are physically complex, ovoid or brick-shaped objects with a complex subvirion structure, which contains an inner core surrounded by a double membrane

• On either side of the core there are lateral glancing bodies composed mostly of protein, and a nucleocapsid, which contains DNA bounded by a layer of protein subunits

• Virion is made up of 30 types of proteins • The complex virions contain all the enzymes necessary for transcription, polyadenylation, and

capping of a specific class of viral mRNAs• Important enzymes are

• RNA polymerase.• Early transcription factors.• mRNA capping enzymes.• mRNA poly(A) polymerase.• RNA helicase.• DNA helicase, ligase, and topoisomerase.• Protein kinase(s)

• The pox virus genome consists of linear double-stranded DNA. The vaccinia virus genome has about 185 kbp and about 180 genes.

• Pox virus DNA is unique because the two strands of the double helix are cross-linked at their termini as a result of phosphodiester bonds between adjacent strands

Replication • It is the only DNA viruses that replicate in a defined area within the host-

cell cytoplasm, a so-called “virus factory”• Entry : receptors for the poxvirus are thought to be Glycosaminoglycans

(GAGs).• Primary un coating

1. Attachment and entry2. Synthesis of early mRNA3. Translation 4. Release of proteins 5. Uncoating and release of nucleoproteins 6. replication of viral genome

7. Synthesis of intermediate mRNA8. Translation of intermediate mRNA9. Synthesis of late mRNA 10. Translation of late mRNA11. Maturation

• On release into the host-cell cytoplasm, the core synthesizes viral early mRNAs which are translated by the cellular protein-synthesizing machinery

• Secondary un coating • Coat disassembly • Early proteins produced, catalys the viral genome replication and expression of intermediate

genes • Intermediate gene products controls late genes • Late genes produce viral capsid proteins and other enzymes • The initial assembly reactions result in formation of the immature virion which is a spherical

particle delimited by a membrane that may be acquired from an early compartment of the cellular secretory pathway.

• This virus particle matures into the brickshaped IMV • The IMV can be released by cell lysis• Or IMVs acquire a second, double membrane from a trans-Golgi or early endosomal

compartment to form the intracellular enveloped virion (IEV) • IEVs move to the cell surface on microtubules where fusion with the plasma membrane forms

cell-associated virions (CEV). These CEV induce an actin polymerization that promotes a direct transfer to surrounding cells or they can also dissociate from the membrane as EEV.

Glycosaminoglycans (GAGs)

• Important genuses are:• Orthopox: Small pox, cow pox, vaccinia, monkey pox• Parapox:• Yatapox• Molluscipox

• Small pox: • Smallpox is an acute contagious disease caused by variola virus, which is believed to

have originated over 3,000 years ago in India or Egypt, was one of the most devastating diseases known to humanity.

• Smallpox is transmitted from person to person by infected aerosols and air droplets spread in face-to-face contact with an infected person.

• Variola major and Variola minor• Smallpox localized in small blood vessels of the skin and in the mouth and throat• In the skin it forms characteristic rash and blisters• In 1967, WHO launched an intensified plan to eradicate smallpox.• Edward Jenner demonstrated, in 1798, that inoculation of humans with live vaccinia

virus (cowpox) could protect against smallpox. • After vaccination campaigns throughout the 19th and 20th centuries, the WHO

certified the eradication of smallpox in 1979.