Virus Assembly, Release, and Maturation

What are the general steps of assembly and release of non-enveloped viruses?

• Capsid formation

• Insertion of genome (can occur with capsid formation simultaneously or after capsid is formed)

• Assembly in cytoplasm or nucleus

• Exit from cell, usually through cell lysis and thus cell death

General steps of assembly and release of enveloped viruses

• Assembly - viral structure proteins associate with the genome to form the core particle

• Viral glycoproteins are targeted at cell membranes

• Core associates with cell membrane at point where there is a large concentration of viral glycoproteins

• Virus buds into cell membrane, typically not resulting in death and thus the virus obtains the envelope

Step 1 of assembly

Formation of structural units, which contain 2-6 protein subunits that associate with each other during synthesis

Concerted assembly

Virus assembles around the genome, which links packaging with assembly

Sequential assembly

Procapsid is formed using scaffolding proteins, a protease degrades the scaffolding proteins forming the capsid, and then the genome is inserted

What is an example of a virus that undergoes sequential assembly?

Herpesvirus

How do viruses selectively package viral genomes over cellular genomes?

• Packing signals in genome directly interact with the viral structural proteins

What would happen if a packaging signal in a DNA virus was mutated?

It would result in an accumulation of empty capsids

How are segmented genomes packaged?

Each segment has a packing signal, regions in N proteins and base pairing between packaging signals contribute to genome packing

What are assembly sites of enveloped viruses decided by?

Insertion and accumulation of viral envelope proteins

What are different ways viruses can induce bending in the membrane?

• Interactions between envelope and capsid

• Multimerization of capsid proteins under the plasma membrane

• Solely by envelope glycoproteins

• By bending matrix proteins and interacting with envelope and ribonucleoproteins

What is the ESCRT pathway, and how do viruses use it?

Endosomal sorting complexes required for transport, viruses use it to mediate budding away from the cytoplasm

Which domains bind and recruit ESCRT proteins?

L domains

What was the first identified virus that uses the ESCRT pathway for release from the membrane?

HIV

What is an example of a virus that does ESCRT independent budding/release? How do they do this?

Influenza, interactions between viral structural proteins and membranes helps them bud and release from the cell

What is unique about herpesvirus assembly and exit?

It obtains and loses multiple envelopes as it exits the cell through the ER/golgi

How are nonenveloped viruses released?

Cell lysis through viroporins typically, or non-lytic route which involves viral release through an autophagosome or multivesicular bodies

How do viruses mature?

After or during assembly, proteolytic processing occurs for some viruses where proteins are cleaved into their final products, Ex. HIV cleavage of Gag and Gag-Pol proteins

How can viruses spread to other cells?

• They can release into their extracellular environment

• spread directly from cell to cell without being exposed through the extracellular environment through cell fusion or synapses in neurons

• Virological synapses