How Do Retroviruses Replicate?

Retrovirus

Retrovirus is an enveloped RNA virus belonging to the viral family Retroviridae. It incorporates a copy of its RNA into the DNA of a host cell that it infects, thereby modifying the genome of that cell.

These viruses are known to be associated with tumor production in different animal species such as cats, fowl, and rodents. Thus, these viruses are also known as RNA tumor viruses.

Structure of a retrovirus

Retrovirus, also known as oncovirus, is an RNA virus that causes cancer in the host. It is enveloped and spherical with 100 nm in diameter. Retrovirus is a host-specific virus. The human immunodeficiency virus which causes acquired immune deficiency syndrome in humans is an example of a retrovirus.

The structure of the virus allows it to attach to the host, inject its genome and replicate by causing infection in the host cell. The main parts of the structure of a retrovirus are:

Structure of a retrovirus. Diagram created in BioRender.com

1. RNA genome

Retrovirus is a positive single-stranded RNA virus. It stores the information for the synthesis of a special enzyme called reverse transcriptase.

2. Reverse transcriptase

It an enzyme produced by retrovirus only. Reverse transcriptase as the name indicates works opposite to transcriptase enzyme. It converts genetic information stored in RNA into a DNA molecule. The DNA formed is then integrated into the host genome and helps in the survival and replication of retrovirus.

3. Protein capsid

The genome of a retrovirus is protected by a protein covering called the capsid. It dissociates and helps in the fusion of viral particles with the host cell membrane.

4. Viral envelope

The viral envelope is taken from the host cell membrane during the budding process. It consists of glycoprotein and lipid molecules.

It protects the nucleocapsid (RNA + capsid) from damages. It is also helpful in the entry and exit from the host cell. The envelope aids in the fusion of viral particles with the cell membrane of the host.

5. Envelope spikes

The spikes are made up of glycoproteins and help in the entry of the virus into the host cell. It binds with receptors, initiates conformational changes, and finally fusion with cell membrane takes place.
For example, in the case of AIDS, HIV binds with CD4 receptors and helps in the fusion, and finally enters the genome into human T-lymphocytes.

Retrovirus is a spherical and enveloped virus. It infects host cells by binding to specific receptors. The unique feature of a retrovirus is the presence of reverse transcriptase enzyme in their nucleocapsid. Reverse transcriptase converts signal-stranded RNA into double-stranded DNA.

This DNA not only causes infection in the host cell but also transferred to the next generation as it becomes incorporated into the host genome. This is why retrovirus is also called a provirus. Provirus can reside in the host body undetected for months or even years before becoming active and causing infection.

Let’s take the example of Human Immunodeficiency Virus (HIV) that causes Acquired immune deficiency syndrome (AIDS) to understand the process of replication of retrovirus.

Human Immunodeficiency Virus (HIV)

AIDS was first reported in the early 1980s in young males who were homosexual. The symptoms of this disease include severe pneumonia, weight loss, vascular cancer, loss of immune functions, and swollen lymph nodes. AIDS was also transferred from patients to healthy persons through blood transfusion.

The virus causing AIDS was first identified in 1984 by a research team from Pasteur institute in France and the National Institute of Health in the USA. The human immunodeficiency virus (HIV), the causative agent of AIDS, infects helper T-lymphocytes and weakens the immune system. As the immune system fails, the infected person becomes vulnerable to other infections. HIV is host-specific and causes diseases only in humans.

The steps involved in the replication of HIV are as follow:

Diagram created in BioRender.com

1. Attachment and fusion to the receptor site

The HIV attaches to cells having a CD4 receptor site on their surface. As HIV infects the immune system, so the cells it attaches are T-lymphocytes, macrophages, monocytes, and dendritic cells. CD4 receptors are involved in the sending of signals about the presence of antigens to the immune system.

After the attachment to the CD4 receptor, HIV envelope fuses with the cell membrane of the host cell, thus allowing the entry of HIV capsid to the cell.

2. Reverse transcription and integration

After the entry into the cell, the reverse transcriptase uses viral RNA as a template and converts it into single-stranded DNA and then double-stranded DNA. The viral RNA is degraded and the proviral DNA then gains entry into the nucleus and integrated into the host genome.

The HIV after integration remains dormant and does not show any infection. This stage is called latency. It is difficult to detect infected cells at the latency stage.

3. Transcriton and translations

After receiving the signal to become active, the proviral DNA uses host RNA polymerase to produces HIV mRNA. The mRNA stores instructions to make new viral proteins and translated them into viral proteins.

4. Assembly and release

The viral proteins combine to form capsid around viral RNA and include reverse transcriptase molecules. After the assembly of the genome and capsid, new virus buds from the cell membrane taking the host cell membrane as an envelope in the process.

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