Question

Describe the retrovirus life cycle, starting with the free virus.

Short answer

The retrovirus life cycle starts with attachment and entry into the host cell via interactions between viral envelope proteins and host cell receptors. Inside the cell, the viral RNA is reverse transcribed into double-stranded DNA (provirus) using reverse transcriptase. The proviral DNA is integrated into the host genome by integrase. The host transcription machinery then transcribes viral genes, and the resulting RNA is translated into viral proteins. The new viral particles assemble at the cell membrane, bud off, and undergo maturation to become infectious.

Step-by-step solution

Introduction to Retroviruses

Retroviruses are a class of RNA viruses with a unique replication mechanism that involves the reverse transcription of their RNA genome into DNA and the integration of this DNA into the host cell's genome. This allows the long-term expression of viral genes and the production of more virus particles.

Attachment and Entry

The retrovirus life cycle begins with the free virus outside the host cell. The virus has envelope proteins on its surface that recognize and interact with specific cell surface receptors on the host cell. This interaction allows the virus to attach itself to the cell. Once attached, the virus envelope fuses with the host cell membrane, allowing the virus core, containing viral RNA and reverse transcriptase, to enter the cell.

Reverse Transcription

Once inside the host cell, the viral RNA is reverse transcribed by the enzyme reverse transcriptase, which synthesizes a complementary DNA (cDNA) from the viral RNA template. The cDNA strand then acts as a template for the synthesis of a complementary DNA strand, resulting in a double-stranded DNA molecule called a provirus.

Integration

The proviral DNA is transported to the host cell nucleus, where it is integrated into the host genome by the viral integrase enzyme, a critical step for the long-term expression of viral genes. The integrated DNA, now a part of the host cell's genome, can be transcribed by the host's transcription machinery like any other cellular gene.

Transcription and Translation

The proviral DNA is transcribed into RNA by the host cell's RNA polymerase. Some of the produced RNA will serve as a template for new viral genomes, while others will be translated into viral proteins. These viral proteins include the structural and envelope proteins necessary for building new virus particles, as well as the enzymes reverse transcriptase and integrase for the next viral life cycle.

Assembly and Budding

The newly synthesized viral proteins and RNA genomes are transported to the cell membrane, where they assemble into new virus particles. The virus particles bud off from the cell membrane, acquiring a lipid envelope from the host cell membrane in the process. This envelope contains viral envelope proteins to facilitate attachment and entry into the next host cell.

Maturation

After the virus particles are released from the host cell, a protease enzyme cleaves the precursor viral proteins into their functional forms. This maturation step is necessary for the infectivity of new virus particles. In summary, the retrovirus life cycle consists of six key steps: attachment and entry, reverse transcription, integration, transcription and translation, assembly and budding, and maturation. Each step is crucial for the successful replication and transmission of the virus to new host cells.

Key concepts

Reverse Transcription

In the intriguing world of retroviruses, reverse transcription stands out as a unique process. Retroviruses are RNA viruses, but their replication depends on converting their RNA genome into DNA.
This task is accomplished by the enzyme reverse transcriptase. Once the retrovirus enters a host cell, it releases its RNA alongside reverse transcriptase into the cell's cytoplasm. The reverse transcriptase then proceeds to synthesize a complementary DNA (cDNA) strand from the viral RNA template.
This is just the beginning, as this cDNA acts as a template for synthesizing a second DNA strand. The result is a double-stranded DNA (dsDNA) molecule called a provirus, marking a pivotal transformation from viral RNA to DNA.

Viral Integration

Following the reverse transcription, the newly crafted proviral DNA is ready for the next major step: integration into the host cell's genome. This integration is orchestrated by the viral integrase enzyme.
The proviral DNA is transported into the host cell's nucleus, where integrase facilitates its insertion into the host's DNA.

• This integration enables the viral DNA to be treated like any other gene within the host genome, transcribing and expressing viral components efficiently.
• The integrated viral DNA ensures that the virus can persist within the host, leading potentially to long-term infection and the production of viral particles whenever the host cell's machinery allows.

This stage is crucial for the virus's ability to hijack host cellular machinery for its replication.

Virus Assembly

Virus assembly is the phase where all the viral components come together to form new virus particles. This process occurs after the necessary viral proteins and RNA genomes have been synthesized through transcription and translation of the integrated viral DNA.
The new viral RNA and proteins are assembled into virus-like structures at the host cell membrane.

• The assembly site is usually the cell's membrane, where structural proteins and RNA genomes converge.
• As the virus assembles, it incorporates components from the host cell's membrane to form its own lipid envelope.

Each newly formed particle then buds off from the host cell, ready to infect new cells. The intricate coordination of incorporating both host and viral components is essential for forming fully functional viral particles.

RNA Viruses

RNA viruses, such as retroviruses, utilize RNA as their genetic material, setting them apart from DNA viruses. Retroviruses are notable due to their "reverse" approach to replication, employing reverse transcription to convert their RNA into DNA.
This versatility in manipulating genetic material allows them to integrate into the host genome and persist in host cells for extended periods.

• RNA viruses are generally known for their high mutation rates, adding to their adaptability and sometimes complicating the development of vaccines.
• Despite these challenges, understanding their replication cycle helps in designing therapeutic strategies and treatments.

This makes them a fascinating subject of study and a target for medical research.

Virus Maturation

Virus maturation is the final stop before a virus is fully capable of infection. After budding off from the host cell, the newly formed virus particles undergo crucial maturation steps.
During this process, protease enzymes play a vital role by cleaving the viral proteins into their functional forms.

• This step is indispensable for rendering the virus particles infectious, as non-matured particles generally lack the ability to effectively infect new host cells.
• Maturation often continues even after the virus has left the original host cell, highlighting its importance in the virus life cycle.

Enabling precise structural and functional readiness of the virus particles, maturation is what equips them for successful invasion into future host cells.