Characteristics of Viruses

Basic Characteristics of Viruses

• Viruses are the smallest infectious agents known to cause disease in humans
• Most viruses are only visible using electron microscopy
• The largest viruses can be seen using a light microscope
• A true virus contains either DNA or RNA as its genome
• Viral genomes are contained within a protein shell
• The type of nucleic acid (DNA or RNA) is a basis for viral classification
• Viruses are incapable of independent metabolism or reproduction
• Viruses are obligate intracellular parasites
• Viruses require living cells to replicate
• Viruses cannot grow or divide on their own
• Viruses divert a cell's metabolic capacities to synthesize viral nucleic acids and proteins
• Viruses use the ribosomes of the host cell to replicate
• Viral replication gets controlled by nucleic acid
• Viruses lack the genetic information to produce energy
• Viruses are specific in their action, infecting particular organs or organisms
• Viruses are unaffected by antimicrobial antibiotics
• Viruses may undergo mutations

General Structure of a Virus

• Nucleic acid gets covered by a protein shell or coat called a capsid, also known as a nucleocapsid
• The capsid consists of clusters of polypeptides called capsomeres
• Some viruses possess an outer envelope, a glycoprotein from the host cell
• A mature, infective virus particle is called a viron
• Most DNA viruses do not possess an envelope, with the exception of herpes viruses
• Most RNA viruses are enveloped, except for picorna viruses and reoviruses

DNA Viruses

• Poxviruses
• Herpes viruses(HSV-1&2, Chickenpox, Epstein Barr Virus (EBV), CMV)
• Adenoviruses
• Paporvaviruses (Papilloma viruses, Polyoma virus, Vacuolating virus)

RNA Viruses

• PICORNAviruses (Polioviruses, Coxsackie virus, ECHO virus (Entero Cytopathic Human Orphan virus))
• Rhinoviruses
• ORTHOMYXO viruses cause influenza
• PARAMYXO viruses(Parainfluenza virus which cause sore throat, Measles virus, Mumps virus, LTTI (Lower Respiratory Tract Infection) virus)
• Rhabdoviruses (Rabies virus)

Viruses and the Target Cell: Pathogenic Mechanisms

• Functional implications of a viral infection arise from changes produced by the viruses in the host cell
• The reaction of the host tissue to changes caused by a virus
• The response of the immune system to both the virus and the cellular changes it produces
• A virus must enter a host cell and replicate within
• Viruses require access to the interior of a host cell for replication
• The steps in viral replication are: attachment, penetration, uncoating, synthesis, assembly, and release

Steps in Viral Replication

• Attachment occurs when the virus contacts its target cell randomly
• Attachment of the virion to the cell surface requires a specific viral receptor site
• The surface membrane of a cell has a specific viral receptor site that is complementary to an attachment site on the virus
• Poliovirus and influenza virus are examples
• Viral penetration occurs after attachment to the plasma membrane through engulfment, known as viropexis
• Penetration is temperature and energy-dependent
• Enveloped viruses fuse their envelope with the plasma membrane
• Nucleocapsid gets released directly into the host cytoplasm
• Uncoating of the virus particle involves removing the protein capsid
• Viral nucleic acid gets uncoated
• Uncoating means exposure of the viral nucleic acid
• Uncoating may never be completed in reoviruses
• Nucleic acid and protein synthesis happens in two stages for DNA viruses, with early proteins synthesized in the nucleus
• Late proteins get synthesized in the cytoplasm
• RNA viruses undergo synthesis in one stage, primarily in the cytoplasm
• Orthomyxoviruses are an exception, which replicate in the nucleus
• Structurally mature viruses undergo assembly
• Viruses get released from the host cell

Viral Latency

• Viruses, herpes viruses in particular, can remain dormant in the host cell for long periods and remain integrated
• A trigger is required to undergo a period of replication after viruses remain integrated

The Effects of Viral Replication

• Viruses on host cells may undergo morphological changes
• Viruses often cause disease by killing infected cells (permissive cells)
• Many viruses produce disease without killing infected cells (non-permissive cells), such as Rota virus
• Symptoms of the common cold are due to the release of bradykinin
• Viruses also produce disease by promoting the release of chemical mediators that incite inflammatory or immunological responses

Effects of Viral Replication on Host Cells

• No change occurs in cells undergoing a latent viral infection, showing no structural abnormalities
• A virus can infect and persist in cells without interfering with their function, a process called latency
• Viruses that establish latent infections can emerge to produce disease or infection after the primary infection
• Opportunistic infections are frequently caused by viruses that have established latent infections
• CMV and HSV are frequent opportunistic pathogens that emerge in persons with impaired cell-mediated immunity
• Cell death is a common outcome of viral infections
• The type of cell affected plays a role in determining the clinical pattern of disease
• Poliomyelitis is an example, where destruction of anterior motor neurons leads to motor paralysis
• Alteration of the cell surface membrane can occur
• Paramyxoviruses cause fusion between infected and non-infected cells, forming multinucleated giant cells
• Multinucleated giant cells are not uncommon in tissues of patients with measles
• Giant cells are found chiefly, but not exclusively, in lymphoid tissues
• Giant cells are useful in the diagnosis of measles in tissue sections from pneumonia patients
• A characteristic of measles is mulberry-like giant cells known as Warthin-Finkeldey cells

Types of Inclusion Bodies

• The formation of inclusion bodies are strongly eosinophilic in tissue sections stained with H&E
• Intracytoplasmic inclusions are found in the cytoplasm of cells infected by:
  • Poxviruses (Guarnieri body)
  • Paramyxoviruses
  • Reoviruses
  • Rhabdoviruses (Negri bodies in the brain and spinal cord) in rabies
• Intranuclear inclusions are found in the nucleus of cells infected by:
  • Herpes viruses
  • Adenoviruses
• Viral infections can cause cells to proliferate, independent of any oncogenic effect
• Proliferation is commonly seen in self-limiting disorders
• Infectious mononucleosis caused by the herpes virus serves as an example
• EBV of the target cell can be found in the B lymphocytes
• The B lymphocytes end up proliferating

Protective Response of Host Cells Against Viral Infections

• The host cell's protective response to viral infections include:
  • Inflammation (lymphocytes or cellular response)
  • Antibody production (humoral response via Immunoglobulins IgG, IgM, IgA)
  • Interferon production (glycoproteins)

Interferon Production

• Interferons are produced by the host cell, especially the macrophage system, in response to viral infections
• Interferons are not antibodies
• Interferons are specific to the species in which they are produced (species specific but not virus specific)

Types of Interferon

• There are three distinct types of interferon:
  • Alpha interferon is released chiefly by leucocytes
  • Beta interferon is released chiefly from fibroblasts
  • Gamma interferon is released by activated T lymphocytes
• Most important inducers of alpha and beta interferon release are viral infections
• Production can also be triggered by Rickettsiae, Protozoa and bacterial endotoxins

Actions of Interferon

• Interferon acts by interfering with viral synthesis
• The protective effect of interferon is not limited to a single virus because, unlike antibodies, does not interact directly with the virus
• Interferon secreted by an infected cell diffuses and binds to a membrane receptor on the surface of neighboring non-infected cells
• There is no inhibition of viral attachment or penetration of the cell to which interferon has bound
• The protective effect gets mediated through blocking the translation of viral mRNA in the host cell polyribosomes

Failure of Viral Elimination

• Failure to eliminate the virus from the host cell can lead to latent infections
• The virus is not normally detected
• The infection persists in occult
• Quiescent from the episode of reactivation in the form of acute, self-limiting illness

Latent Infections

• Examples include HSV, herpes zoster virus (HZV) which causes shingles or herpes zoster, and chicken pox which causes varicella
• Persistent and slow infection happens when viral elimination fails, the infection persists and causes a prolonged disease
• Examples include HBV, HCV, and CMV
• Oncogenic infections incorporate part of the viral genome into the host genome, resulting in malignant transformation or cancer

Oncogenic

• Examples of DNA viruses are:
  • Papilloma viruses, such as squamous cell papilloma, condyloma accuminatum, and carcinoma of the cervix (HPV)
  • Herpes viruses, such as Burkitt’s lymphoma and nasopharyngeal carcinoma (EBV)
  • Hepatitis B virus (HBV) which may lead to hepatocellular carcinoma
• Examples of RNA oncogenic viruses include:
  • Hepatitis C virus (HCV) which may lead to Hepatocellular carcinoma
  • Human T cell Lymphotropic Virus-1 (HTLV-1) which may lead to Adult T cell leukemia