2.3 Viruses Flashcards
(37 cards)
Animal viruses: Influenza: Genome
8 segments of single-stranded RNA
The RNA genome is a negative-strand
RNA is packaged with protein into a helical nucleoprotein form with 3 segments coding for 3 different polymerases that form the RNA dependent RNA polymerase which functions in both replication and transcription
the other 5 segments code for haemagglutinin [HA], neuraminidase [NA], nucleoprotein [NP], matrix protein M1 [M] and non-structural proteins [NS]
Animal viruses: Influenza: Capsid
protein lining the inner side of the envelope
Animal viruses: Influenza: Envelope
The influenza virion is an enveloped virus that derived its lipid bilayer from the plasma membrane of a host cell
HA and NA are embedded in the envelope
different types of HA and NA glycoproteins give rise to different strains of influenza virus
Animal viruses: Influenza: Attachment
HA on influenza virus binds to sialic acid receptor on host cell membrane
Animal viruses: Influenza: Penetration and uncoating
Influenza virus enters by endocytosis; the host plasma membrane invaginates and pinches off, placing the virus in an endocytic vesicle/ endosome
The vesicle fuses with a lysosome causing its pH to drop
low pH environment stimulates the viral envelope to fuse with lipid bilayer of the vesicle membrane and nucleocapsid is released into the cytoplasm
The capsid is degraded by cellular enzymes leaving behind the helical nucleoprotein which enters the nucleus of the cell
Animal viruses: Influenza: replication
The viral genome (-) is used as a template to synthesise the viral mRNA/ (+) strand RNA catalysed by RNA dependent RNA polymerase
mRNA produced acts as template to synthesise new viral RNA genome
the mRNA strands then exit the nucleus into the cytosol and RER where they are translated into structural components such as glycoproteins to be incorporated into the viral envelope (at RER) and capsid proteins (in cytosol)
Animal viruses: Influenza: Maturation
Viral glycoproteins are transported by the vesicles from the ER and are incorporated into the plasma membrane
Capsid proteins associate with these glycoproteins at the plasma membrane
The viral genome associates with proteins to form the helical nucleoprotein which interacts with the capsid proteins at the plasma membrane of the host cell
Interaction of the capsid with the nucleoprotein initiates the budding process
Animal viruses: Influenza: Release by budding
Each new virus buds from the cell (evagination)
It acquires the host membrane with viral glycoproteins embedded
With enveloped viruses, host cell may or may not be lysed
The release is facilitated by neuraminidase which cleaves sialic acid from the cell surface and progeny virions, facilitating release from infected cells
Animal viruses: HIV: Genome
2 copies of single-stranded RNA
(+) strands i.e. the viral genome
RNA is tightly bound to proteins; nucleocapsid proteins
HIV genome contains three major genes: 5’-gag-pol-env-3’ encoding major structural proteins as well as essential enzymes
gag: structural proteins (capsid, matrix, nucleocapsid protein)
pol: viral enzymes (reverse transcriptase, integrase, HIV protease)
env: glycoproteins gp120 and gp41
Animal viruses: HIV: Capsid
The capsid is usually conical shaped and made of another type of proteins different from the nucleocapsid proteins
Within the capsid are 2 molecules of enzyme reverse transcriptase which transcribes RNA into DNA, integrase and protease
capsid + viral genome = virus core
Animal viruses: HIV: Envelope
Glycoproteins gp120 and gp41 protrude through the envelope and have a specific conformation that allows the virus to bind to certain receptors on T4 helper cells
Animal viruses: HIV: Attachment
gp120 on the surface of the viral particle interacts with the CD4 receptor on the target cell (T-lymphocytes and macrophages) with the help of a co-receptor
Animal viruses: HIV: Penetration and uncoating
With the help of gp41, the viral envelope will fuse with the host cell membrane and the capsid is then released into the cell, leaving the envelope behind
The capsid and nucleocapsid protein are degraded, releasing viral enzymes and RNA into the cytoplasm
Animal viruses: HIV: replication
Viral reverse transcriptase enzyme catalyses the conversion of viral RNA to DNA [Reverse transcriptase will first catalyse synthesis of a DNA strand complementary to the viral RNA strand to form a RNA-DNA hybrid]
RNA strand is degraded and second DNA strand complementary to the first is synthesised to form a double-stranded DNA molecule
Viral DNA enters the host cell nucleus where it is integrated into the genetic material of the host. It is now known as a provirus. The enzyme integrase catalyses this process. Once the viral DNA is integrated into the host genetic material, it may persist in its latent state for many years.
Activation of the host cell results in transcription of viral DNA into viral RNA which serves as the mRNA
mRNA exits the nucleus into the cytoplasm where it is translated into viral polyproteins
Envelope glycoproteins gp120 and gp41 are made in the ER and vesicles will transport them to the cell membrane
Viral RNA also forms the genetic material for the next geenration of viruses
Animal viruses: HIV: Maturation
Polyproteins and HIV genomic RNA assemble at the inner surface of the plasma membrane of the host cell
Animal viruses: HIV: Release
After assembly at the plasma membrane, the virus bus off/evaginates from the cell
The viral envelope is derived from the host cell membrane containing gp120 and gp41
Polyproteins will be cleaved into functional proteins by HIV protease
The functional proteins include structural proteins (matrix, capsid, nucleocapsid proteins) and viral enzymes (reverse transcriptase, integrase, HIV protease)
The virion is now considered matured and ready to infect another cell
Define antigenic drift
A mechanism of variation by viruses that involves the accumulation of mutations in the genes encoding the surface glycoproteins of the virus. The resulting viruses have surface antigens or glycoproteins that have a different conformation from the previous virus strain
How does antigenic drift lead to the increase in spread of viruses?
The new virus strain cannot be recognised by antibodies against previous strains making it easier for them to infect the host and spread throughout a partially immune population
What leads to antigenic drift?
- Lack of proof reading ability of RNA-dependent RNA. polymerase
- Fast/ High rate of replication of the virus
What virus does antigenic drift generally occur on? Briefly explain.
Influenza (A&B)
Sites recognised on haemagglutinin and neuraminidase proteins by host immune systems are under constant selective pressure
Antigenic drift allows for evasion of these host immune systems by small mutations in the haemagglutinin and neuraminidase genes that make the protein unrecognisable to pre-exisiting host immunity
Define antigenic shift
A process whereby there is a sudden and major change in the surface antigens of a virus. The genetic change that enables a flue strain to jump from one animal species to another
When does antigenic shift occur?
It occurs when two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains
Why does antigenic shift occur?
Antigenic shift occurs because the genome of the virus is segmented, allowing for major genetic changes of type by re-assortment of its segmented RNA genome
How does antigenic shift lead to the increase in spread of viruses?
The human immune system has difficulty recognising the new influenza strain, most people do not have pre-existing antibody protection to these novel viruses
The new strain may further evolve to spread from person to person and this could cause the formation of a highly virulent virus and a flu pandemic may arise