What’s the Difference between Viruses, Viroids and Virusoids?

Kaushik Bharati, PhD

What are Viruses?

Viruses are a unique and distinct group of infectious agents that are characterized by their simple, acellular organization and mode of reproduction. They are essentially non-living entities in the outside (extracellular) environment, and can only reproduce inside a living cell. The viruses hijack the host cell machinery for the synthesis of new virus particles, which are usually released by lysis of the host cell. A complete virus particle or virion consists of a single or double stranded DNA or RNA genome (but not both), enclosed in a protein coat called a capsid. Some viruses have additional coatings that are very complex and consist of carbohydrates, lipids as well as other proteins.

Viruses come in various shapes and sizes, and range from about 10 – 400 nm in diameter. The smallest viruses like the φX174 phage and picornavirus are slightly larger than ribosomes, while the largest viruses, the poxviruses, which includes the vaccinia virus are about the same size as the smallest bacteria, and therefore can be viewed under a light microscope. However, most viruses can only be viewed by using a scanning or transmission electron microscope. Some common examples of viruses and the diseases they cause in humans include Hepatitis B virus (HBV) (causes hepatitis, hepatocarcinoma), Human Immunodeficiency Virus (HIV) (causes AIDS), rhinovirus (causes common cold), influenza virus (causes flu), polio virus (causes polio), human papilloma virus (HPV) (causes cervical cancer), paramyxoviruses (causes mumps, measles), rabies virus (causes rabies), Japanese encephalitis virus (JEV) (causes Japanese encephalitis), Yellow Fever virus (causes Yellow Fever), dengue virus (causes dengue) and many others.

What are Viroids?

Viroids are even simpler infectious agents than viruses. Viroids infect plants and are made up of only RNA. These particles are covalently closed, circular, single-stranded RNA molecules (ssRNAs) about 250 – 370 nucleotides long. The circular RNA are normally rod-like in shape due to intrastrand base pairing, which gives rise to double-stranded regions with single-stranded loops. Sometimes, viroids are found in the nucleolus of infected host cells, where between 200 – 10,000 copies could be present, while others may be present in the chloroplasts. It should be noted that the RNA of viroids does not encode any gene products. Therefore, they cannot replicate by themselves. It is believed that viroids are replicated by the host cell’s DNA-dependent-RNA polymerase. The host polymerase uses the viroid RNA as a template for RNA synthesis as opposed to the host DNA. The host polymerase synthesizes a negative-sense complementary RNA molecule that serves as a template for the same host polymerase to synthesize the viroid’s new positive-sense RNA by a rolling-circle-like mechanism.

Viroids cause over 20 different plant diseases, including potato spindle-tuber disease, chrysanthemum stunt disease and exocortis disease of citrus plants. Viroids can cause latent infections in some plants, while in other plants, the same viroid can cause severe full-blown disease. Although the pathogenicity of viroids is not well understood, it has been established that certain regions of the RNA are required for infection. Studies have indicated that if these RNA regions are deleted, the disease does not manifest. Experimental evidence indicates that viroids cause disease by triggering a eukaryotic response called RNA silencing, which normally protects against infection by double-stranded RNA (dsRNA) viruses. In this phenomenon of RNA silencing, the host cell detects the presence of dsRNA and degrades it. Viroids can utilize this response by hybridizing with specific mRNA molecules of the host cell, which are complementary to the viroid ssRNA. Formation of the viroid:host mRNA double-stranded hybrid elicits RNA silencing, which results in the destruction of the host message and therefore silencing of the host gene. Failure to express a host mRNA that is complementary to the viroid ssRNA will lead to disease in the infected host plant.

The most well studied viroid is the potato spindle-tuber viroid (PSTV), which has a RNA genome consisting of only 359 nucleotides that is much smaller than any virus genome. Several PSTV strains have been isolated, which differ in pathogenicity, capable of causing mild to severe disease.

What are Virusoids?

Virusoids were previously known as satellite RNAs and are similar to viroids as they also consist of RNA only. Their genome is made up of covalently closed, circular ssRNA molecules with regions capable of intrastrand base pairing. Virusoids, in contrast to viroids, can encode one or more gene products, and they typically require a helper virus in order to infect host cells. The helper virus provides the gene products and other molecules for the virusoid to complete its replication cycle. The best known virusoid is the hepatitis D virusoid, which has a genome of 1700 nucleotides. It uses the hepatitis B virus as its helper virus.

How Do They Differ?

From the foregoing discussion, it is evident that although viruses, viroids and virusoids are similar, there are distinct differences also. While viruses can have a DNA or RNA genome covered by a protein capsid, viroids and virusoids consist of naked RNA. While viruses come in various shapes and sizes, viroids and virusoids are covalently closed circular RNA molecules. Viruses can infect plants, animals and humans, while viroids infect plants and virusoids generally infect animals and humans. While virusoids require a helper virus to establish infection, viruses and viroids do not. These are the basic criteria that differentiate these three simple, acellular, sub-microscopic pathogenic entities.