A virus is a small infectious agent that replicates inside the cells of other organisms. Examples of common diseases caused by viruses include the common cold, influenza, and chickenpox (varicella-zoster virus).
Once an infection has begun it provokes an immune response from the host that typically eliminates the invading virus – this same immune response can also be generated using “dead” or “deactivated” viruses, which is taken advantage of in vaccination.
This article shall discuss basic viral structure, viral replication, and how viruses avoid detection by the immune system.
Viral Structure
Viruses can range in size from as small as 20nm to 300nm, and all viruses share the same basic features:
- DNA or RNA core (never both)
- Protein coat made up of individual capsomeres
- Helical, cubic, or more complex arrangement
- No cytoplasm
- May have an envelope derived from the host cell
- Requires an intracellular organism to replicate
Viral Replication
Viruses can only multiply inside living cells and require a host cell to survive. The host cell must contain the required machinery to synthesise the viral proteins and nucleic acids.
Viral replication occurs in several stages, namely;
- Attachment – The virus becomes attached to the cell by specific cellular receptors which can be glycoproteins, phospholipids or glycolipids.
- Entry – Following attachment the virus can enter the cell, most commonly via receptor-mediated endocytosis. This is the same process by which many hormones enter the cell.
- Uncoating – Once inside the host cell, the viral capsid must be uncoated to release the viral nucleic acid. Uncoating may be achieved by host or viral enzymes that will degrade the capsid.
- Replication – Once uncoated, viruses (DNA or RNA) replicate by switching the host machinery from cellular protein synthesis to viral synthesis, and viral proteins are produced.
- Assembly – Newly synthesised viral proteins are post-transcriptionally modified and packaged into virions that can be released from the infected host cell to infect other cells.
- Release – Virions are released from the cell either by lysis or budding. In lysis, the infected cell dies and the virions are released. In budding, the virion takes some of the host cell’s membrane with it as it leaves – this normally does not kill the infected cell.
Evasion of the Immune System by Viruses
Viruses are continuously evolving – this is one of their greatest strengths for evading the immune system. Mutations in many different viral sites may be used, including changing the proteins at binding sites for antibodies: this is called antigenic drift. Viral mutation has also meant that developing efficacious viral vaccines is extremely challenging.
Another strategy used by some viruses is that of latency – slowly growing and remaining dormant in cells can make it difficult for the immune system to recognise them, as used by the herpes viruses.
Furthermore, viruses can interact with the host immune system to make it less effective, such as through the production of immunosuppressive molecules that impair immune function.
Clinical Relevance – Human Immunodeficiency Virus/AIDS
Human Immunodeficiency Virus (HIV) infects immune cells (particularly CD4+ T cells), thus suppressing the immune system and leading to AIDS (Acquired Immunodeficiency Syndrome). The virus is transmitted through:
- Contact of infected bodily fluids with mucosal tissue/blood/broken skin
- Sharing of needles by intravenous drug users
- Medical procedures: blood/blood –products, skin grafts, organ donation
- Pregnancy/ during delivery
The HIV virus is a type of retrovirus, typically gaining access to CD4+ T cells using a protein called gp120 on its viral envelope to attach to the CD4 molecule of the T cell; assisted by the T cell co-receptor CXCR4. The virus enters the cell and is combined into the host cell’s genome using the viral integrase enzyme.
The virus undergoes reverse transcription and single strands of viral RNA are converted into double-stranded DNA by the viral reverse transcriptase enzyme. The virion is then assembled, buds, and leaves the host cell, ready to infect other cells.
In the first one to two weeks following HIV infection, there are typically flu-like symptoms, later followed by seroconversion; this is when antibodies to HIV can first be detected in the blood. After acute HIV infection, the viral load and CD4+ T cell count remain relatively stable until the virus progresses into clinical AIDS.
Once AIDS has developed the levels of CD4+ T cells decline steadily, leading to opportunistic disease and eventual death.
Nowadays there are a number of effective treatments for HIV that can significantly prolong life and halt the progression of disease. Treatment for the disease is Antiretroviral Therapy (ART), aimed at targeting virally encoded proteins that are essential for viral replication but are absent from normal human cells. The therapy involves a combination of different medications to minimise the risk of the virus evolving to evade the treatment.