Lecture 12!
Virus Host Interaction I
1) The virus growth phases:
=Attachment
- this is the phase where the virus attaches itself to its host cell and before more viruses are made for infection.
=Eclipse stage
- no infectious virus are present in this stage, therefore resulting in a fall in virus titre
- it is the period where the virus attempts to gain control of it's host synthetic machinery and produce components vital for viral assembly
- no virus would be detected in an external medium until release
=Latent stage
- it is the period following the eclipse phase from the time the infecting virus disappearing to the appearance of infectious virus in the surroundings
- virus exist internally and must be released to be assayed
- animal viruses may not have a classic burst of viruses but rather release virus slowly over a long period of time it is possible to find large internal pools of virus
=Virus burst
- new progeny virus is assembled and released
- virus yield (determined on the number of virus released per cell) increases sharply
Additional note: Productive infection is defined as any infection that resulted in production of more infectious particles at the end than at the start.
2) The general virus replication cycle involves six steps where each step is crucial for successful replication. They are:
= Attachment
= Penetration
= Uncoating
= Replication
= Assembly/Maturation
= Release
Stages of attachment, penetration and uncoating gives rise to the Eclipse period mentioned above.
= ATTACHMENT. This is where the specific viruses' attachment protein (VAP) attaches itself to the corresponding host cell receptor. The receptor on the host cell then mediates viral entry into the host cell.
RECEPTORS on host cell can be any surface molecule of the cell (glycoprotein and glycolipid). There are multiple receptors for different viruses, all with their own functions and which viruses use for attachment. Host range is defined based on receptor ligand recognition.
= PENETRATION (ROUTES OF HOST ENTRY) methods include:
- receptor-mediated endocytosis (the cell absorbs material from outside the cell by engulfing it with its cell membrane) for enveloped viruses
- clarthin for naked viruses
- fusion, which is also known as direct penetration
= UNCOATING of the virus refers to the release of infectious nucleic acid from the protein coat. Penetration and uncoating can occur simultaneously, as the nucleic acid enters the host and the protein capsid remains outside.
= REPLICATION. The genome replication and gene expression are very closely linked. Their characteristics depend on the nature of the genome. This brings us to the Baltimore classification, where viruses are classified by their genome.

= Class 1: Double-stranded DNA (ds DNA)
->Two groups:
- replication is EXCLUSIVELY NUCLEAR; very dependent on host cell factors
- replication in the CYTOPLASM; viral genome contains all factors for genome replication and transcription (poxviridae)
->Viral genes
- immediate genes
- Transcription factors / enzymes
- Replication factors/enzymes
-> Early genes
- Additional factors to regulate transcription, replication and translation
- Have some structural proteins
-> Late genes
- Mainly structural proteins
- Other proteins associated with virion / nucleocapsid
= Class II: Single-stranded DNA (ss DNA)
- replication of genome in nucleus- forms double-stranded DNA to make new single-stranded daughters
- extreme parasitism. (dependence on superinfecting viruses for early regulatory genes or chemical or UV light that induce similar virus-induced changes to the host cell)
- one example: Parvoviridae
= Class III: Double-stranded RNA (ds RNA)
- genome in several fragments
- replication, transcription, translation all regulated separately
- monocistronic mRNA
- activity takes place only in cytoplasm, not nucleus
= Class IV: Single-stranded POSITIVE RNA
- Most of the animal and plant viruses are categorised under Class IV
- Group 1
- Polycistronic mRNA
- Polyprotein formed and cleaved
- Group 2
- Complex transcription process
- 2 rounds of translation before formation of genomic RNA
= Class V: Single stranded NEGATIVE RNA
- Group 1:
- Non-segmented genome
- transcription of negative RNA by RNA-dependent RNA polymerase to give monocistronic mRNA, which acts as a template for genome replication
- ambisense organisation
- Group 2:
- Orthomyxoviruses (segmented genome)
- Monocistronic mRNA in nucleus
- Virus transcriptase in nucleocapsid
= Class VI: Single-stranded RNA (ssRNA)
- Retroviruses (example: HIV)
- has a DNA intermediate
- Diploid
- Viral RNA is reverse transcripted to dsDNA by viral RT
- dsDNA is integrated into host genome
- mRNA is not used as viral RNA
= Class VII: Double-stranded RNA (dsRNA)
- has a RNA intermediate
- overlapping reading frames
- example: Hepadnaviridae
= REGULATION OF EXPRESSION. Post-translational modification of the virus protein often occurs here. Polycistronic mRNA is spliced in a differential rate in the nucleus in post-transitional control. The post-translational modification of the viral proteins often occurs, this is also known as maturation. mRNA travels from the nucleus to the cytoplasm.
References:
http://www.ucalgary.ca/~ceri/cmmb421prot/Virus%20Life%20Cycle.html
http://en.wikipedia.org/wiki/Virus