Question

Describe the life cycle of retroviruses.

Short answer

The life cycle of retroviruses consists of eight stages: (1) Attachment, where viral surface proteins interact with host cell receptors; (2) Entry, facilitated by viral envelope glycoproteins, allowing the virus to enter the host cell; (3) Reverse Transcription, where viral RNA is converted into DNA by reverse transcriptase; (4) Integration, in which the newly formed cDNA is integrated into the host cell's genome by integrase; (5) Transcription, during which host cell machinery generates new viral RNA from the provirus; (6) Translation, where viral RNA is translated into viral proteins by ribosomes; (7) Assembly, as new virus particles form and undergo maturation; and (8) Release, where mature virions exit the host cell through budding and continue infecting other cells.

Step-by-step solution

1. Attachment

Attachment is the first step in the life cycle of retroviruses. During this stage, the virus's surface proteins, known as envelope glycoproteins, interact with specific receptors found on the host cell's plasma membrane. This initial interaction allows the virus to attach itself to the host cell, preparing for the next stage: entry.

2. Entry

Entry follows attachment and occurs when the virus enters the host cell. This process is mediated by the viral envelope glycoproteins, which facilitate fusion between the viral envelope and the host cell's plasma membrane. Once the two membranes have fused, the viral core containing the viral RNA and other proteins is released into the host cell's cytoplasm.

3. Reverse Transcription

Retroviruses are unique in that they contain RNA as their genetic material, rather than DNA. In this stage, reverse transcription, the viral RNA is converted into DNA by the viral enzyme reverse transcriptase. This newly synthesized DNA is called complementary DNA (cDNA).

4. Integration

After reverse transcription, the double-stranded cDNA is transported into the host cell's nucleus, where it is integrated into the host cell's DNA. This process is facilitated by the viral enzyme called integrase, which incorporates the cDNA into the host genome. The integrated viral DNA is referred to as a provirus.

5. Transcription

Once integrated into the host cell's genome, the provirus serves as a template for the generation of new viral RNA. Host cell machinery, such as RNA polymerase, transcribes the proviral DNA, generating full-length viral RNA, which serves as the template for new viral protein synthesis and genomic RNA in the progeny virions.

6. Translation

Following transcription, the viral RNA is transported from the nucleus into the cell's cytoplasm. Here, host cell ribosomes translate the viral RNA, producing viral proteins required for the assembly and maturation of new virus particles.

7. Assembly

Assembly is the stage during which new virus particles are formed. The viral proteins and genomic RNA interact and assemble at the host cell's plasma membrane, forming immature virus particles. These immature particles undergo additional processing and maturation steps, during which time the virus acquires its distinct morphology.

8. Release

The final step in the life cycle of retroviruses is the release of mature virions from the host cell. This process, known as budding, occurs when the mature virus particles push outwards, enveloping themselves with a portion of the host cell's plasma membrane. The released virions are now capable of infecting other host cells, thus continuing the replication process.

Key concepts

Viral Entry

The entry phase is an essential step in the retrovirus life cycle where the virus successfully infiltrates the host cell. After attachment, facilitated by the virus's envelope glycoproteins, the viral envelope fuses with the host cell's plasma membrane. This fusion allows the contents of the virus, known as the viral core, to be released into the cytoplasm of the host cell. The viral core consists of viral RNA and proteins which are crucial for subsequent stages in the life cycle. This entry step ensures that the viral genetic material is inside the host cell, paving the way for the next stage of reverse transcription.

Reverse Transcription

Once inside the host cell, retroviruses undergo reverse transcription. This is a distinctive process where the viral RNA genome is transformed into DNA. Retroviruses do this using an enzyme called reverse transcriptase. The DNA formed is known as complementary DNA or cDNA. Reverse transcription is pivotal because it allows the retroviral genetic material to be compatible with the host's cellular machinery. Without this conversion, the virus would be unable to integrate into the host's genome. This phase is critical to the virus's ability to persist and replicate within the cell.

Integration

Integration is a crucial stage where the newly synthesized cDNA enters the host cell's nucleus. Here, another viral enzyme, integrase, comes into play. Integrase helps insert the viral DNA into the host's genome, turning it into a permanent part of the cell's genetic material. This integrated form is referred to as a provirus. The provirus can lie dormant or become active, starting the transcription of viral genes. Integration ensures the virus has a stable blueprint within the cell, allowing for continuous replication during active phases and transmission to daughter cells during cell division.

Viral Assembly

Viral assembly is the stage in which a new generation of virus particles begins to take shape within the host cell. After the viral RNA and proteins are produced, they come together primarily at the host's plasma membrane. This gathering involves the encapsulation of genomic RNA by viral proteins to form immature virus particles. These particles undergo further processing, known as maturation. This step ensures that the viral components are correctly organized, preparing them for release as mature virions capable of entering and infecting other cells. The assembly of viral particles is vital for the continuation of the viral life cycle.

Budding

The final step in the retrovirus life cycle is budding, where newly formed virus particles exit the host cell. During budding, the virus particles move to the surface of the host cell, pushing through and wrapping themselves in portions of the host's plasma membrane, forming a new viral envelope. This process not only releases mature virions into the extracellular space but also allows them to carry the necessary components for infecting other host cells. Budding is an essential step that completes the viral replication cycle and facilitates the spread of infection to other susceptible cells.