Retrovirus

Introduction

Viruses are ubiquitous infectious agents containing genetic material enclosed within a protein coat. Genetic material is either DNA or RNA. Retroviruses contain RNA as the genetic material and are grouped under the family Retroviridae. Retroviruses have become the subject of interest with the discovery of the enzyme called reverse transcriptase. Its discovery by Temin and Baltimore has led to the identification of a new family of viruses “Retroviridae” that was not known till then. Retroviruses have distinguishing characteristics that mark them different from other viruses. They are known to cause infections, cancers, and inflammatory diseases in humans.

What is a Retrovirus?

All the viruses containing a linear and single-stranded RNA (ssRNA) enclosed in a lipid layer are placed under a separate family called Retroviridae and those viruses are called retroviruses.

Some consider retroviruses as the group of viruses that insert the DNA copy of its RNA genome into the host cell DNA. This is possible by an enzyme called reverse transcriptase.

The presence of both single-stranded RNA and reverse transcriptase is the unique identification mark of the Retroviruses.

Examples are human immunodeficiency virus (HIV), human T lymphotropic virus type- 1 (HTLV1), human T lymphotropic virus type-2 (HTLV2), Rous sarcoma virus and murine leukaemia virus.

Retrovirus Structure

• Each retrovirus contains two copies of ssRNA that occur as a dimer with complementary base pairing at the kissing loop complex.

• Surrounding them are the associated proteins (nucleocapsid proteins, enzymes). A proteinaceous capsid outlines associated proteins.

• Capsid shape varies with species. It is either spherical, conical or cylindrical. Exterior to the capsid is the viral envelope. Capsid and viral envelope are separated by matrix proteins.

• Viral envelope protects inner genetic material. The envelope has transmembrane proteins bound to surface glycoproteins. These surface glycoproteins help host cell recognition and attachment.

  

Retrovirus Life Cycle

• Retroviruses infect healthy host cells by attaching their surface glycoproteins to host cell receptors. This binding initiates changes in transmembrane proteins allowing the fusion of virion with the host cell.

• After successful viral entry, the enzyme reverse transcriptase synthesizes a DNA copy of the viral genome. The newly synthesized DNA copy is called a provirus and is associated with certain viral proteins.

• The provirus is transported into the host cell nucleus as a preintegration complex. Within the nucleus, the provirus is incorporated into host DNA by the action of the integrase enzyme. It cuts the host DNA and seals the ends of the provirus with the host DNA cut ends.

• The viral genes are expressed along with host DNA. The newly produced viral proteins and RNAs assemble together forming new virus particles.

• They are ready for the next infection cycle on healthy host cells.

• The stages of infection are considered the early phase while the viral gene expression is considered the late phase in the retrovirus life cycle.

Retrovirus Replication

• After integration of the provirus into host DNA, the viral genes may or may not be expressed.

• In case they are not expressed, the viral genes replicate along with the host DNA and all the new host cells formed contain viral genome copies. This is a latent infection.

Retrovirus Genetic Material

The single-stranded RNA molecule of retroviruses is around 7 to 12 kb in length.

Most retroviruses contain four genes namely pol, env, gag, and pro. Each gene products have its significance.

• The pol gene encodes enzymes like reverse transcriptase, integrase, and RNaseH.

• The env gene encodes the surface glycoproteins and transmembrane proteins. On a whole, the env genes are responsible for the viral receptor binding and successful entry into the host.

• The gag genes encode a polyprotein called Gag with structural functions like the assembly of non-infectious viral particles into a complete infectious virion.

• The pro genes encode protease enzymes that are required for viral particle maturation.

Retroviral Vectors

• Vectors are the biological vehicles designed for delivering the target genes to treat genetic disorders and cancers.

• Retroviruses are genetically engineered to deliver selected genes. Lentiviral vectors and murine leukaemia viral vectors are some examples of retroviral vectors.

• Retroviral vectors containing a good copy of the defective genes are constructed using biotechnological tools. Patient stem cells are infected with these retroviral vectors. Retroviruses integrate their genome into the host cell genome and replicate along with it. Hence, as the stem cells divide they contain a good copy of the gene.

Difference Between Virus and Retrovirus

Virus	Retrovirus
Genetic material is either DNA or RNA.	Genetic material is strictly RNA.
The viral genome is directly inserted into the host genome in a pathogenic cycle.	A DNA copy of the retroviral genome is synthesized prior to insertion into the host genome.
Virions produced in all generations are the same copies of the genome.	Virions produced in the second and further generations have minor genomic differences because of inaccuracy in reverse transcription.
Finding treatments for viral infections is comparatively easier.	Finding effective treatments is difficult because of the changes in the genome in subsequent generations.

Conclusion

Retroviruses contain two copies of linear, single-stranded RNA segments as the genetic material. They have specialised membrane proteins that aid their attachment to a suitable host cell. After entry into the host cell, retroviruses synthesize a DNA copy of their genome by using the enzyme reverse transcriptase. This is the marking feature of Retroviridae members and sets them apart from all other viruses. Retroviruses are known to cause many diseases in humans and animals. HIV and HTLV-1 are popularly known disease-causing retroviruses. Retroviral vectors like lentiviral vectors and murine leukaemia vectors have significant applications in treating genetic as well as oncological diseases.

FAQs

Q1. Why are retroviruses called so?

Ans. Information flows from DNA to RNA in living organisms. In retroviruses, DNA is synthesised from the RNA by a reverse transcription process. The name Retrovirus is coined based on this behaviour. Retro (Latin) means backward

Q2. Can retrovirus replicate in absence of a host cell?

Ans. Retrovirus integrates a DNA copy of its genome into the host genome and it is the only possible way for expressing its genes. So, a retrovirus needs a suitable host cell for replication and cannot produce numbers in the host cell’s absence.

Q3. How is AIDS treated?

Ans. AIDS is caused by HIV, a retrovirus. Patients diagnosed with AIDS are subjected to antiretroviral therapy (ART). Antiretroviral drugs mainly block viral multiplication by inhibiting reverse transcriptase and protease enzymes.

Q4. What are oncogenic retroviruses?

Ans. Oncogenic retroviruses cause cancer when they integrate the provirus into host genes that are potent to cause cancer. Some examples are the Rous Sarcoma virus and the Avian leukosis virus.

Q5. What are the disadvantages of retroviral vectors?

Ans. The possible disadvantage associated with the retroviral vectors is that they undergo random insertions into the host genome which can lead to oncogene activation due to insertional mutagenesis.