Reproduction of positive-sense single-stranded RNA viruses

Initiation of the infectious process

The first stage of reproduction is the penetration of the virion into the host cell. This process occurs via receptor-mediated endocytosis — the virus binds to specific cellular receptors, after which the cell membrane invaginates, engulfing the viral particle.

Once inside the cell, the virus undergoes deproteinization, or «uncoating». The protein coat breaks down, releasing the viral genome — the positive-sense RNA strand — directly into the cytoplasm of the infected cell. It is in the cytoplasm that all subsequent events of the viral cycle will unfold.

Early translation: immediate protein synthesis

The key feature of this group of pathogens lies in the nature of their nucleic acid. The released genomic plus-RNA is structurally ready to function as messenger RNA (mRNA). It binds directly to cellular ribosomes.

The process of early translation proceeds as follows:

• Ribosomes read the information from the viral RNA and synthesize a single giant polyprotein.
• This polyprotein cannot function in this form and undergoes enzymatic cleavage.
• As a result of cleavage, four non-structural proteins (NSP 1–4) are formed.

The most important of these non-structural proteins is RNA-dependent RNA polymerase, an enzyme critically required for the next stage, since the host cell itself is incapable of synthesizing RNA on an RNA template.

Viral genome replication

Having acquired its own polymerase, the virus proceeds to large-scale copying of the genetic material. The viral polymerase uses the initial genomic plus-RNA as a template for transcription.

First, a complementary negative-sense RNA strand is synthesized. It does not encode proteins and serves exclusively as a template. Based on this minus strand, the enzyme actively produces two types of RNA molecules:

1. Full-length copies of genomic plus-RNA (49S). These are full-size genetic molecules that will be packaged into new progeny virions.
2. Incomplete (subgenomic) 26S mRNA molecules. These shortened strands are needed exclusively to trigger the massive synthesis of the structural elements of the future virus.

Structural protein synthesis and modification

The assembly of a complete virion requires different types of proteins, so their production is strictly distributed within the cellular space:

• Capsid C-protein is produced on free ribosomes floating in the cytoplasm. It rapidly accumulates and prepares to meet new copies of the genome.
• Envelope glycoproteins (E1–3) are synthesized on ribosomes tightly bound to the membranes of the endoplasmic reticulum (ER).

The synthesized glycoproteins are immediately embedded into the ER membrane. Then they undergo a complex pathway of intracellular transport: they travel to the Golgi apparatus, where they undergo additional glycosylation (addition of carbohydrate residues). The final chord of this stage is the movement and embedding of fully finished viral glycoproteins into the plasma membrane of the cell.

Nucleocapsid assembly and virion release

At the final stage, new viral particles are formed. The capsid C-protein finds the newly synthesized genomic RNA in the cytoplasm and tightly binds to it. This forms the nucleocapsid.

Next, the nucleocapsid moves to the inner side of the plasma membrane of the cell. It purposefully interacts precisely with those areas of the membrane that have already been modified and contain embedded viral glycoproteins.

The process ends with budding. The nucleocapsid pushes a section of the cell membrane outward, gradually wrapping itself in it. As a result, a complete virion covered with a lipid envelope containing viral spikes (glycoproteins) pinches off from the cell. Meanwhile, the cell performs a peculiar form of exocytosis, releasing new viruses to infect neighboring tissues.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of receptor-mediated endocytosis of viral particles
• Features of polyprotein cleavage into non-structural proteins (NSP 1–4)
• Differences between the full genome copy (49S) and subgenomic mRNA (26S)
• The process of post-translational modification and glycosylation in the Golgi apparatus
• Molecular mechanisms of nucleocapsid interaction with the plasma membrane during budding

Other topics in the "Microbial Physiology" section

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