Viruses are genetic elements that cannot replicate independently of a living host cell. Host cells provide energy and metabolic intermediates needed for the replication and synthesis of viral proteins. As viruses need suitable living cells to multiply, viruses are called obligate intracellular parasites.
Viruses exist in either extracellular or intracellular forms. The extracellular form of a virus is called a virus particle or virion, which is a microscopic particle-containing nucleic acid surrounded by a protein coat. Virion is metabolically inert and cannot generate energy or carry out biosynthesis. Virus particle facilitates the transmission of the virus from one host cell to another.
The entire virus, including nucleic acid, capsid, envelope, and glycoprotein spikes, is called the virion, or a virus particle.
Once a virus enters a new host cell, its intracellular state begins, and the virus starts replication. Using host cells’ structural and metabolic components, the virus forms new copies of virus genomes, parts of virus coat, and does assembly of new virions. Eventually, progeny viruses leave the host cell either by budding or the lysis of the host cell.
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Size and Shape of Viruses
Virions come in many sizes and shapes. Most viruses are smaller than prokaryotic cells, ranging in size from 0.02 to 0.3 μm (20–300 nm). Because of this small size, viruses can pass through bacterial filters and can not be visualized by a light microscope.
Viruses are extremely small, so the common unit of measure for viruses is the nanometer, which is one-thousandth of a micrometer.
- Smallpox virus, one of the largest viruses, is about 200 nm in diameter (about the size of the smallest cells of Bacteria).
- Poliovirus, one of the smallest viruses, is only 28 nm in diameter (about the size of a ribosome).
Most animal viruses are roughly spherical with some exceptions.
- Rabies virus: Bullet shaped
- Ebola virus: Filamentous shaped
- Poxvirus: Brick shaped
- Adenovirus: Space vehicle shaped
The structures of virions are quite diverse, varying widely in size, shape, and chemical composition.
Viruses are composed of a nucleic acid genome surrounded by a protein shell called a capsid. Together the genome and capsid are referred to as the nucleocapsid.
This protein coat is composed of a number of individual protein molecules called capsomers. A few viruses have only a single kind of protein in their capsid, but most viruses have several distinct proteins. Capsomers are arranged in a precise and highly repetitive pattern around the nucleic acid. The capsomere is the smallest morphological unit seen with the electron microscope.
A single virion can have a large number of capsomeres. The information for proper folding and assembly of the proteins into capsomeres is typically contained within the structure of the proteins themselves; hence, the overall process of virion assembly is called self-assembly. The virus nucleocapsid is the complete complex of nucleic acid and protein packaged in the virion.
The nucleocapsids of viruses are constructed in highly symmetric ways. Three kinds of symmetry are recognized in viruses, helical, icosahedron, and complex.
- Helical symmetry: Rod-shaped viruses have helical symmetry. Examples, tobacco mosaic virus (TMV), measles, mumps, influenza, rabies, etc.
- Icosahedral symmetry: The icosahedron pattern is the most efficient arrangement for subunits in a closed shell. Spherical viruses have icosahedral symmetry. It is a symmetric structure roughly spherical in shape and contains 20 faces (each an equilateral triangle). There are exactly 60 identical subunits on the surface of an icosahedron. Most viruses are built with icosahedral symmetry. For example, polioviruses, adenoviruses, etc.
- Complex symmetry: These are viruses with complex or uncertain symmetries. For example, smallpox virus has the most complex virion structure consisting of many different proteins and lipoproteins. Bacteriophages are the most complicated viruses in terms of structure as they contain icosahedral heads and helical tails.
Although viruses are acellular entities, they possess a genome that encodes information required for viral replication. Viral genomes are smaller than those of most cells. The largest known viral genome is Mimivirus, which consists of 1.18 Mbp of double-stranded DNA and is larger than some cellular genomes. Some viruses have genomes so small they contain fewer than five genes.
Viruses have DNA or RNA genomes (in contrast, all cells contain double-stranded DNA genomes). Viruses can be classified according to whether the nucleic acid in the virion is DNA or RNA and further subdivided according to whether the nucleic acid is single (ss) or double-stranded (ds), linear, or circular.
Viruses are the only creatures with genetic material composed of single-stranded DNA and double-stranded RNA.
- Viruses having double-stranded RNA as their genome: viruses of the family Reoviridae (Rotavirus, Colorado tick fever virus) and Birnaviridae have double-stranded RNA as their genome.
- Viruses having single-stranded DNA as their genome: virus of the family Parvoviridae (Parvovirus B-19) possesses single-stranded DNA.
- RNA can exist in several pieces. Influenza virus and rotavirus have a segmented RNA genome
- Almost all viruses are haploid, i.e. they contain a single copy of the genome with a major exception of retrovirus family which is diploid (have two copies of their RNA genome).
Most viral genomes are linear but some viral genomes are circular. Viruses whose genomes consist of DNA follow the central dogma of molecular biology but RNA viruses are exceptions to this rule. Regardless of the genome structure, all viruses must synthesize messenger RNA (mRNA) which is then translated by the host cells’ translational machinery (ribosomes).
Some viruses are naked (non-enveloped viruses are called naked), whereas others possess lipid-containing layers around the nucleocapsid called an envelope.
Enveloped viruses contain a membrane surrounding the nucleocapsid. The viral envelope consists of a lipid bilayer, derived from the membranes of the host cell. Embedded in it are viral membrane proteins, usually, glycoproteins, coded by viral genes. Glycoprotein spikes extend from the surface of the virus and act as attachment projections or as enzymes (e.g., neuraminidases).
As the envelope of a virion makes initial contact with the host cells, it controls the specificity of virus infection. The virus-specific envelope proteins are critical for the attachment of the virion to the host cell during infection. Virus attaches to specific receptors on the host cell membrane via their glycoprotein spikes. The specificity of this interaction determines the host and cells within the host.
Virions that have envelopes are sensitive to lipid solvents such as ether and chloroform. Their capacity to infect cells is inactivated by these solvents. Naked viruses are not affected by lipid solvents.
Enzymes in Virions
Although most virions lack their own enzymes, some virions contain one or more virus-specific enzymes. Such enzymes play a role during the infection and replication processes. Some of the common viral enzymes and their roles are summarized in the table below.
|Name of the enzyme||Virions carrying it||Functions|
|Lysozyme||Bacteriophage||Bacteriophage use lysozyme to make a small hole in the bacterial cell wall, through which they inject their nucleic acid into the host cell cytoplasm. Lysozyme produced during later stages of bacteriophage infection helps to lyse the bacterial cell wall and release progeny viruses.|
|RNA-dependent DNA polymerase (reverse transcriptase)||Retroviruses||Reverse-transcriptase transcribes the viral RNA to form a DNA intermediate|
|RNA polymerases||RNA viruses||Because cells cannot make DNA or RNA from an RNA template|
|Neuraminidases||Certain animal viruses||Cleave glycosidic bonds in glycoproteins and glycolipids of animal cell connective tissue and aid the release of virions from the host cells.|
Clinically important common viruses and diseases caused by them are listed in this table;
|Name of the virus causing disease||Name of the disease or conditions|
|Herpes simplex virus types 1 and 2||Painful vesicles on the face and genitals|
|Varicella-zoster virus||varicella (chickenpox)typically in children and, zoster (shingles)|
|Epstein-Barr virus||Infectious mononucleosis|
|Human herpesvirus 8||Kaposi’s sarcoma|
|Hepatitis B virus||Viral hepatitis|
|Adenovirus||Both URTI and LRTI (mostly, pharyngitis and pneumonia)|
|Papillomaviruses||Papillomas on the skin and mucous membranes; some strains cause carcinoma of cervix.|
|Parvovirus B19||Slapped cheek syndrome|
|Rabies virus||Rabies (fatal encephalitis)|
|Hepatitis C virus||Chronic hepatitis and predisposes to hepatic carcinoma|
|Human T-cell Lymphotropic virus||T-cell leukemia and tropical spastic paraparesis|
|Human Immunodeficiency virus||AIDS|
|Poliovirus||Polio (aseptic meningitis and paralysis)|
|Rotaviruses||Gastroenteritis in young children|
|Hepatitis A virus||Hepatitis|
|Noroviruses||Gastroenteritis especially in adults|
|Hepatitis E virus||Hepatitis acquired by the fecal-oral route|
Lab Diagnosis of Viral Infections
The diagnosis of a viral infection can be established in several ways, often used together, namely:
- Detection of virus particles in a specimen taken from the appropriate site.
- Detection of viral antigens (Ag) in blood or body fluids
- Serological procedure to detect specific anti-viral antibodies (rise in antibody titer or presence of IgM antibody) or detection of the presence of cell-mediated immune response.
- Detection of viral nucleic acids in the blood or body cells of a patient
- Culture of infectious virus from an appropriate clinical specimen.
- Presence of viral cytopathic effect (CPE) in cytological or histological examination of cells from the site of the infection
Microscopic identification of Viruses
Viruses can be detected and identified by direct microscopic examination of clinical specimens such as biopsy materials or skin lesions. Three different microscopy techniques are currently in use:
- Light microscopy: It reveals characteristic inclusion bodies or multinucleated giant cells. e.g. Tzanck smear which shows herpesvirus induced multinucleated giant cells (MGCs) in vesicular skin lesions.
- UV Microscopy: It is used for fluorescent antibody staining of the virus in infected cells.
- Electron Microscopy: It detects virus particles, which are further characterized by their size and morphology.
Serological procedure for the laboratory diagnosis of Viruses
- A rise in antibody titer to the virus can be used to diagnose viral infection. A serum sample is obtained in the acute phase (as soon as viral etiology is suspected), and a second sample is obtained in the convalescent phase (10-14 days later). If the antibody titer in the convalescent-phase serum sample is at least four fold higher than the titer in the acute phase serum sample, the patient is considered to be infected.
- In some viral diseases for which cutoff titer is known, patients showing a rise in antibody titer than cut off value can be considered as infected and
- In other viral diseases, the presence of IgM antibodies is diagnostic. Primary antibody response is governed by IgM (predominately produced).
Detection of Viral Antigens
Various tests such as ELISA, EFA etc can detect the presence of viral antigens in the patient blood or biopsy materials. For the diagnosis of Hepatitis virus infection, HBsAg (Hepatitis viral surface antigen) or HBeAg (Hepatitis virus e antigens) can be detected. Similarly, detection of p24 viral antigen is the diagnostic method in case of HIV Infection.
Detection of Viral Nucleic acids
Detection of viral nucleic acids is one of the sensitive and rapid methods for laboratory diagnosis. It requires the use of PCR (polymerase chain reaction) to amplify the viral genome present in the sample and detection of the specific gene sequence of that particular virus by the use of a specific primer (while performing PCR) and probe (while detecting the specific sequence). RNA viral assay is currently used to monitor the course of HIV infection and evaluate the patient progress.
Identification of the virus in the cell culture
Viruses are obligate intracellular parasites, so we cannot grow them in ordinary media (like we grow bacteria and fungi) and require living cells for the growth and propagation. The growth of the virus in the cell culture may produce a characteristic cytopathic effect (CPE) which helps us for presumptive diagnosis. If that particular virus does not produce the cytopathic effect, its presence can be detected by several other techniques such as Immunofluorescence assay (e.g. DFA, IFA), Radioimmunoassay (RIA), Hemadsorption, decrease in acid production of infected cells, ELISA, Complement fixation, Hemagglutination inhibition method, neutralization, etc.
References and further readings
- Review of Medical Microbiology & Immunology: A Guide to Clinical Infectious Diseases, 15e Levinson W, Chin-Hong P, Joyce EA, Nussbaum J and Schwartz B. Lange, Mc Graw Hill.
- Madigan Michael T, Bender, Kelly S, Buckley, Daniel H, Sattley, W. Matthew, & Stahl, David A. (2018). Brock Biology of Microorganisms (15th Edition). Pearson.
- Louten, J. (2016). Virus Structure and Classification. Essential Human Virology, 19–29. https://doi.org/10.1016/B978-0-12-800947-5.00002-8