Retrovirus Cycle: 9 Facts You Should Know

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Retroviruses

The retroviruses are the class of viruses having RNA as their genome and can insert its genome in the host DNA, this step is crucial for the life cycle of a retrovirus or the retrovirus cycle hence changing the genome of the host cell. After entering the host cytoplasm, retrovirus synthesizes cDNA from genomic RNA using its enzyme reverse transcriptase. This process is unusual and reverse of the normal transcription process, hence reverse transcription. The virus is known as retrovirus (retro means “backward”). The cDNA formed in the reverse transcription process is integrated into the host cell genome with an enzyme known as integrase.

After this step, the retroviral DNA is known as the provirus. The provirus is now a part of the host cell genome. It undergoes replication, transcription, and translation and the host cell DNA. The provirus is capable of producing and assembling new copies of the virus by following the retrovirus cycle.

Retroviruses are classified into three subfamilies:

  • Oncoretroviruses: these are the oncogenic viruses that cause several types of cancers.
  • Lentiviruses are commonly known as slow retroviruses that cause immunodeficiencies in several organisms.
  • Spumaviruses are also known as foamy viruses, and they do not cause disease.

Some serious diseases caused by retroviruses in humans and other animals include:

  • Cancer in mouse is caused by murine leukemia virus (MLV)
  • Various diseases in humans are caused by human T-lymphotropic viruses (HTLVs)
  • Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV)

Provirus

It is a viral genome integrated into the DNA of the host cell. Similar to the case of bacteriophages, proviruses are frequently called prophages. But, the slight difference between the provirus and prophage is that even if the host cell is in the condition of stress, a provirus does not detach (excise) from the host genome, unlike a prophage. 

A provirus may exist in the state of an inactive endogenous viral element, or it can undergo replication. The inactive endogenous viral elements do not replicate themselves until the host cell genome replication process starts. All the daughter cells of the infected host will then contain the provirus. The inactive state could last for many generations of the host cell. The endogenous retrovirus always remains in the provirus state. This process of virus multiplication is known as lysogenic reproduction.

The integration of the viral genome in the host cell DNA usually results in a productive or latent infection.

Productive infection: provirus starts transcribing mRNA to produce new copies of the virus by hijacking the host’s cellular machinery. An increase in the virus’s copies inside the host cell results in the lysis of its cell membrane. The virus particles are released after the lysis of the host cell. They can infect the other neighboring cells of the host body.

Latent infection: provirus remains transcriptionally silent most of the time. But, provirus becomes transcriptionally active with the change in the host’s health and environmental conditions. The change results in the switching of latent to productive infection.

Nearly 8% of the human genome comprises proviruses and inherited endogenous retroviruses. Several prokaryotic viruses also integrate genome into their prokaryotic host cell like eukaryotic viruses. Prokaryotic proviruses generally replicate when the whole circular chromosome replicates.

Retrovirus vs. provirus

The key differences among proviruses and retroviruses are as follows:

Proviruses

  • It’s a viral genome integrated with the host genome
  • It’s a stage of replication of the virus
  • They do not contain reverse transcriptase enzyme

Retroviruses

  • It’s an RNA virus that has the ability to synthesize cDNA from RNA by the process of the reverse transcription
  • They are single-stranded RNA viruses
  • They contain an enzyme known as reverse transcriptase
retrovirus cycle
Figure (Retrovirus cycle): Life cycle of retrovirus
https://commons.wikimedia.org/wiki/File:Hiv_gross.png

Retrovirus cycle

The life cycle or replication of retroviruses is unique compared to the other organisms. The replication cycle of the retrovirus is completed in the following phases:

Infection: the retroviruses come in contact with the host and infect the host body’s normal cells.Internalization: the RNA genome of the retrovirus makes an entry into the host cell cytoplasm.

Reverse Transcription: in the host cell cytoplasm, the process of reverse transcription takes place. The cDNA is produced from the viral RNA genome with the help of an enzyme known as reverse transcriptase, and the process is known as reverse transcription.

The cDNA is then made entry into the host cell’s nucleus through the nuclear pore complex.

Integration: the cDNA (viral DNA) now integrates itself with the host cell genome with the help of an enzyme known as integrase

Viral Gene Expression: viral genes are then transcribed to form mRNA, which later undergoes translation to produce viral proteins.

Release of viral particles: viral particles are then released from the host cell by rupturing the host cell’s cell membrane (lytic phase). 

Infection spreads: the viral particles released from the host cells then infect the neighboring host cells. 

Viral RNA

The RNA also contains genetic information similar to the DNA. Several viruses (specifically retroviruses) contain RNA genome, and they are often regarded as RNA viruses. Their RNA genomes translate to encode a variety of proteins. Some of these proteins are often involved in the replication, transcription, and reverse transcription of the viral RNA genome. Some of the proteins protect the viral RNA/genome when the viral particle contacts the host. Viroids are pathogens composed of RNA molecules alone; they are replicated inside the host plant body with the help of plant cell’s RNA polymerase. Viroids do not code for any protein.

RNAs are the crucial bio-macromolecule present in retroviruses. They are generally involved in protein synthesis and carry the genetic information from DNA outside the nucleus essential for maintenance.  

The genetic material of HIV consists of

The HIV (Human immunodeficiency virus) is a retrovirus that causes AIDS (Acquired immunodeficiency syndrome) which fails in the body’s immune system. The condition of AIDS makes our body more susceptible to pathogenic infections and even responsible for the prognosis of several types of cancers. HIV is a retrovirus and belongs to the Retroviridae family. Its called a retrovirus because, unlike all the other viruses, they store their genetic information in RNA rather than DNA, and with the help of an enzyme known as reverse transcriptase, they make a copy of cDNA (complementary DNA) from their RNA genome as soon as they enter into the host cell.

They acquire host cellular machinery to synthesize or reproduce viral particles. The HIV has two copies of the positive-sense single-stranded RNA (+ssRNA) as their genome enveloped by a conical capsid of proteins. Furthermore, HIV contains enzymes like integrase, ribonuclease, protease, and reverse transcriptase, which are required to develop retrovirus. 

HIV strc
Figure (retrovirus cycle): HIV genome and structure
“HIV Virion Structure” (CC BY 2.0) by NIAID

RNA viruses require their own supply of certain enzymes because

Retroviruses (RNA viruses) contain RNA as their genetic material or genome. In contrast, the host body cells contain DNA as their genome. To integrate the genome into the host cell DNA, retrovirus synthesizes cDNA from its RNA genome by reverse transcription. The enzyme reverse transcriptase is involved in this process and needs an RNA template to synthesize cDNA. For the sake of synthesizing cDNA from RNA, retroviruses carry their own enzymes for replication and recombination of the viral genome with the host cell DNA as the host cell DNA does not have genes for such enzymes.

Teminism

It’s a theory based on reverse transcription (mainly occurs in retrovirus cycle). Teminism is used to explain that the RNA can also act as a template for cDNA formation. The process starts as soon as the retrovirus enters the host’s body. The process of reverse transcription operates in the cytoplasm of host cells. The RNA from the retrovirus makes entry into the nucleo-protein complex. The reverse transcription process produces a linear DNA duplex having long terminal repeats (LTRs), commonly known as terminal duplications. The terminal duplications are not present in the retroviral RNA genome.

According to the central dogma:

DNA –> mRNA –> Protein

The DNA codes for mRNA by the transcription process, and this mRNA further codes for protein by the process of translation.

Teminism is the only known exception of the central dogma exhibited by retroviruses. The viruses containing the RNA genome experience a phase in their life cycle. Their RNA is used as the template to synthesize DNA by the enzyme reverse transcriptase action. Their ability to perform reverse transcription is very often utilized in the field of molecular biology.

teminism 1
Figure (retrovirus cycle): Teminism is the only exception of central dogma https://commons.wikimedia.org/wiki/File:Extended_Central_Dogma_with_Enzymes.jpg

RNA enzymes

RNA enzymes (Ribozymes) are the RNA molecules exhibiting the capability to catalyze several biochemical pathways’ reactions. RNA enzyme facilitates reaction such as Splicing of RNA (a post-translational modification in eukaryotes). In the year 1982, it was revealed for the first time that RNA acts as a bio-catalyst like enzymes, and it also acts as genetic material. This was further supported with the RNA world hypothesis, which suggests the importance of RNA in the evolution of the pre-biotic autonomously replicating (self-replicating) systems.

The ribozymes are also involved in the peptide bond formation, ligating, and cleaving DNA and RNA complex. RNA enzymes are involved in linking ribosomal RNA (rRNA) of the ribosome’s large subunit with the amino acids during translation and protein synthesis. RNA enzymes are also involved in the tRNA (transfer RNA) biosynthesis and replication of viruses. Hairpin ribozyme, leadzyme, VSribozyme, and hammerhead ribozymes are common examples of RNA enzymes.

Ribozyme 1
Figure (retrovirus cycle): catalytic action of ribozyme
https://commons.wikimedia.org/wiki/File:Ribozyme.jpg

Conclusions

This article covers the retroviral life cycle aspects and the difference between proviruses and retroviruses. To know more about retroviruses and reverse transcriptase, click here

FAQs

Q1. What makes the reverse transcriptase process less accurate and error-prone Is there any way we can make it more accurate?

Answer: Since reverse transcriptase lacks the ability to proofread the polymerized product, the process of reverse transcription is very prone to errors. Engineered reverse transcriptase can solve the problem of errors.

Q2. Is reverse transcriptase not used by the normal cell in the human

Answer: Our body has a specific type of reverse transcriptase known as telomerase responsible for the synthesis of telomeric DNA. 

Q3. Does anyone know how a retrovirus like HIV can make dsDNA from 2 +ssRNA molecules and a reverse transcriptase

Answer: retroviruses are characterized by the presence of enzyme reverse transcriptase and RNA genome. They produce dsDNA from ssRNA with the help of enzyme reverse transcriptase and then integrate their genome into the host genome. Then integrated retroviral genome (provirus) transcribes and translates with the viral particles (retrovirus cycle). 

Q4. When reverse transcriptase reads the RNA, does it read from 3′ to 5′

Answer: reverse transcriptase binds to the 5′ end of the RNA template. It synthesizes DNA in the direction 5’–> 3.’

But reads the RNA template in the direction 3’–> 5.’

Q5. Can a reverse transcriptase transcript an mRNA into DNA

Answer: Yes, it can synthesize DNA from mRNA. Specifically, reverse transcriptase is often used to construct cDNA libraries from mRNA templates.

Q6. Which viruses are retrovirus

Answer: The viruses containing RNA as their genome are known as retroviruses. 

Q7. Is ribozyme a protein

Answer: Ribozymes are RNA molecules, and in some cases, they may vary by RNA-Protein complexes. Ribosomes are catalytically active.

Q8. Are retrovirus infection always incurable and lethal 

Answer: spumaviruses (a class of retroviruses) do not cause diseases. Not all retroviral infections are lethal. 

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