Retrovirus

Retrovirus replication initiates with the attachment of viral envelope proteins to specific receptors on host cell membranes. Subsequently, the virus fuses with the host cell membrane, releasing viral RNA into the cytoplasm. The enzyme reverse transcriptase converts the viral RNA into DNA, which then integrates into the host cell’s genome.

Host cellular machinery transcribes the integrated viral DNA into RNA, translating it into viral proteins. In this article, we will study the structure, life cycle, and replication of retrovirus with examples.

What is Retrovirus?

Definition of Retrovirus: A retrovirus is a type of RNA virus that replicates by converting its RNA genome into DNA which is then integrated into the host cell’s genome.

Retrovirus is a virus that belongs to the family of Retroviridae. It uses RNA as its genetic material, and when it infects a cell, it uses an enzyme called reverse transcriptase to convert its RNA into DNA. This newly formed DNA is then integrated into the host cell’s genome, where it can remain dormant or become active. It leads to the production of viral proteins and, ultimately, the assembly of new viral particles.

This replication process is complex and can lead to persistent infections. Many retroviruses are associated with diseases, including AIDS and some forms of cancer. Retrovirus is divided into different subfamilies, which is further divided into three major groups:

• Oncoretroviruses (oncogenic retroviruses)
• Spumaviruses (foamy viruses)
• Lentiviruses (slow retroviruses)

Structure of Retrovirus

Retroviruses are spherical particles, usually 100–200 nanometers in diameter, that have an envelope and a core. The structure of the retrovirus is explained in detail below:

• Envelope: Retroviruses are enveloped viruses, meaning they are surrounded by a lipid membrane derived from the host cell.
• Envelope Proteins: Embedded within the lipid envelope are viral glycoproteins, including surface glycoprotein (SU) and transmembrane protein (TM), which facilitate attachment and fusion with host cell membranes.
• Capsid: Inside the envelope, retroviruses contain a protein shell called the capsid, which encloses the viral RNA genome and associated proteins.
• RNA Genome: Retroviruses carry their genetic information in the form of single-stranded RNA molecules. This RNA serves as the template for replication and transcription.
• Reverse Transcriptase (RT): Retroviruses encode the enzyme reverse transcriptase, which catalyzes the conversion of viral RNA into DNA during replication.
• Integrase: Another viral enzyme, integrase, is responsible for integrating the viral DNA copy into the host cell’s genome during the replication process.
• Protease: Protease is an enzyme that cleaves viral polyproteins into functional proteins, facilitating the assembly of new viral particles.
• Terminal Repeat Sequences: Retroviral genomes contain repeated sequences at both ends, called long terminal repeats (LTRs), which play roles in replication, integration, and transcriptional regulation.
• Matrix Protein: Matrix proteins are associated with the inner surface of the viral envelope and play a role in virus assembly and budding.
• Nucleocapsid Protein: Nucleocapsid proteins bind to the viral RNA genome within the capsid, protecting it and help in viral replication processes.

Retrovirus Genome

Retroviruses are a type of virus that use RNA as their genetic material. They are named for the enzyme reverse transcriptase, which is a vital part of their life cycle. This RNA genome typically ranges from around 7,000 to 12,000 nucleotides in length. Retroviruses are “retro” because they reverse the normal gene-copying process. 

Usually, cells convert DNA into RNA so that it can be made into proteins. But with retroviruses, the process has to start by going backward. Once a retrovirus infects a cell, it converts its RNA into DNA through reverse transcription. The viral DNA is then inserted into the host cell’s DNA, where it begins replicating.

Retrovirus Life Cycle

The life cycle of a retrovirus can be divided into two phases: the early phase and the late phase. The early phase includes the steps of infection from cell binding to the integration of the viral cDNA into the cell genome. The late phase begins with the expression of viral genes.

In the retrovirus life cycle, the virus integrates its genetic material into the host cell’s DNA using integrase. During host cell DNA transcription, viral DNA is transcribed into RNA, which guides the production of new viral proteins. These proteins help in assembling new virus particles, which bud off from the host cell and are released to infect other cells.

Retrovirus Replication Steps

Retroviruses, like HIV, have a unique replication process that combines lytic and lysogenic elements. The steps of retrovirus replication are:

The virus binds to the target cell. (Binding)

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The membranes of the virus and the cell fuse. (Fusion)

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The capsid shell uncoats and the viral genome is reverse transcribed from ss-RNA into ds-DNA. (Uncoating)

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The genome integrates with the target cell. (Integration)

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The host transcribes the DNA back into RNA. (Transcription)

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Viral mRNA is produced, translated into proteins, and assembled into new viruses. (Translation )

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Protease matures the viruses before they infect other cells. (Maturation)

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The new viruses bud off with an envelope. (Release)

Difference Between Retrovirus And Virus

The difference between retrovirus and virus are:

Feature	Retrovirus	Virus
Genetic Material	Single-stranded RNA	Can be DNA or RNA
Replication	Requires reverse transcription to convert RNA into DNA	Replicates using host cell machinery or viral enzymes
Integration	Integrates its DNA into the host cell’s genome	Typically does not integrate into host genome
Host Range	Infects a wide range of species, including humans and animals	Can be specific to certain species or cell types
Disease Types	Can cause various diseases, including cancer (oncogenic viruses)	Can cause a wide range of diseases, including cancers
Examples	HIV, HTLV, Visna-Maedi virus	Influenza virus, herpes simplex virus, adenovirus

Retroviral Vectors

Retroviral vectors are modified retroviruses used as tools in genetic engineering and gene therapy. These vectors are designed to deliver specific genes into target cells by taking advantage of the retroviral life cycle. Retroviral vector is characterised by their ability to integrate the transgene into the host cell’s genome, resulting in stable and long-term gene expression. Retroviral vector design involves:

• Replication-competent vectors: Adding sequences to existing viruses.
• Replication-defective vectors: Replacing retroviral sequences.
• Gene insertion: Permitting synthesis of full-length copies of the vector genome.
• Vector spread: Replacing most or all of the coding regions of a retrovirus.

Retroviral Vectors Advantages and Disadvantages

Some of the advantages and limitations of retroviral vectors are given below:

Retroviral vectors have several advantages, including:

• Infection is not lytic to cells.
• The transduced DNA is stably integrated into host cell chromosomal DNA.
• Expression from DNA integrated by retroviral infection is much more efficient than from transfected DNA.

Some limitations of retroviral vectors include:

• Safety: The production of replication competent virus, which can infect humans.
• Retroviral titre: The low titre produced by the packaging cells.
• Gene expression: The lack of gene expression in vivo because of the methylation of viral promoters.

Retrovirus Examples

Retroviruses are a family of viruses that are classified by their structure and how they replicate in a host. Some examples of retroviruses are:

Human immunodeficiency virus (HIV)

Human immunodeficiency virus (HIV) is a virus that weakens the body’s immune system by destroying cells that fight disease and infection. HIV spread through contact with certain bodily fluids of an infected person, including blood, breast milk, semen, and vaginal fluids. It does not spread by kisses, hugs, or sharing food. HIV can also spread from a mother to her baby. If left untreated, HIV can lead to AIDS, the late stage of HIV infection when the body’s immune system is badly damaged. There is currently no cure for HIV, but it can be controlled with proper medical care.

Human T-lymphotropic virus type 1 (HTLV-1)

Human T-lymphotropic virus type 1 (HTLV-1) is a virus that infects T cells, a type of white blood cell, and can cause leukemia and lymphoma. It’s also known as human T-cell leukemia virus type 1, or adult T-cell lymphoma virus type 1. HTLV-1 is spread by sharing needles or syringes, through blood transfusions, or from mother to child during birth or breastfeeding. 

Human T-lymphotropic virus type 2 (HTLV-2)

Human T-lymphotropic virus type 2 (HTLV-2) is a retrovirus that can infect cells of the monocyte/macrophage lineage. It’s associated with rare hematologic malignancies, such as atypical hairy cell leukemia, large granular lymphocytic leukemia, and mycosis fungoides.

Endogenous Retrovirus

Endogenous retroviruses (ERVs) are remnants of retroviruses that are no longer infectious. They are a part of the genome and are similar to exogenous retroviruses, but are not infectious. ERVs are important components of the antiviral immune response. They regulate cellular immune activation and may even directly target invading viral pathogens. ERVs are also involved in pathological processes such as virus infection, immune response, and aging.

ERVs may be beneficial to the host, but could also be harmful. They may be involved in certain autoimmune diseases and cancers. ERVs are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome.

Conclusion: Replication of Retrovirus

Retroviruses are a large and diverse family of RNA viruses that use reverse transcriptase to transcribe RNA into DNA. They are distinguished from other viruses by the presence of reverse transcriptase. Retrovirus replication occurs when a retrovirus enters a host cell and the reverse transcriptase enzyme converts the retroviral RNA genome into double-stranded DNA. This DNA then migrates to the nucleus and becomes integrated into the host genome. The viral genes are transcribed and translated, and new virus particles assemble, exit the cell, and infect others.

FAQs on Replication of Retrovirus

What are Retroviruses?

Retroviruses are a large family of viruses that use RNA as their genetic material instead of DNA. They are distinguished from other viruses by the presence of reverse transcriptase, an enzyme that transcribes RNA into DNA.

Name a Retrovirus in Humans?

Human T-cell leukemia virus (HTLV) is a retrovirus found in humans that is associated with various diseases, including adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis.

How does a Retrovirus Work?

Retroviruses are viruses that use RNA as their genetic material. When a retrovirus infects a cell, it converts the retroviral RNA into DNA. This DNA is then inserted into the host cell’s DNA, and the cell produces more retroviruses that infect other cells.

How can a Retrovirus be Treated?

Retrovirus infections are treated with antiretroviral drugs, which act on different stages of the HIV life cycle. A combination of three or four antiretroviral drugs is known as highly active antiretroviral therapy (HAART).

What Causes Retroviral Infection?

Retroviral infections are caused by retroviruses, which are RNA viruses that can integrate their genetic material into the host cell’s genome, leading to persistent infections.

What is HIV or What Causes AIDS?

HIV (Human Immunodeficiency Virus) causes AIDS (Acquired Immunodeficiency Syndrome) by progressively damaging the immune system, leaving the body vulnerable to opportunistic infections and cancers.

What is the 4 Steps of Viral Replication?

Viral replication involves attachment, penetration, replication of viral components, and release of new virions from the host cell.

What are the 4 Retroviruses?

The four retroviruses are Human Immunodeficiency Virus (HIV), Human T-cell Leukemia Virus (HTLV), Murine Leukemia Virus (MLV), and Avian Leukosis Virus (ALV).