🦠Virology Unit 8 – Human Viral Pathogens – DNA Viruses
DNA viruses are a diverse group of pathogens that cause various human diseases. These viruses contain DNA genomes, replicate in the host cell nucleus, and employ complex strategies to evade immune responses and persist in the body.
Understanding DNA viruses is crucial for developing effective treatments and prevention methods. From common cold sores to cancer-causing infections, these viruses significantly impact human health and require ongoing research to combat their effects.
DNA viruses contain a genome composed of double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA)
Possess a protein capsid that encases and protects the viral genome
May have an additional lipid envelope derived from the host cell membrane
Replicate within the nucleus of the host cell, utilizing host cell machinery for transcription and replication
Cause a wide range of diseases in humans, including respiratory illnesses, skin infections, and various cancers
Examples of DNA viruses include Herpesviruses (Epstein-Barr virus), Adenoviruses, and Papillomaviruses (Human Papillomavirus)
Viral Structure and Genome
DNA viruses have a genome made of DNA, which can be linear or circular, and single-stranded or double-stranded
Linear genomes have free ends, while circular genomes form a continuous loop
Double-stranded DNA is more stable and less prone to mutations compared to single-stranded DNA
Genome size varies among DNA viruses, ranging from a few kilobases (kb) to hundreds of kilobases
Viral capsid is composed of multiple copies of one or more types of capsid proteins, which self-assemble to form a protective shell around the genome
Capsid proteins are encoded by the viral genome and synthesized during replication
Some DNA viruses (Herpesviruses) have an additional lipid envelope surrounding the capsid, which is derived from the host cell membrane during the budding process
Structural proteins, such as tegument proteins in Herpesviruses, may be present between the capsid and the envelope, providing additional functions in the viral life cycle
Replication Cycle
Attachment: Viral surface proteins (capsid or envelope proteins) bind to specific receptors on the host cell surface
Entry: Viruses enter the cell through endocytosis or fusion with the cell membrane, releasing the capsid into the cytoplasm
Uncoating: The viral capsid is disassembled, exposing the viral genome
Replication: The viral genome is transported to the nucleus, where it is transcribed and replicated using host cell machinery
Early genes are expressed first, encoding proteins required for viral genome replication and regulation of host cell functions
Late genes are expressed after genome replication, encoding structural proteins for new virion assembly
Assembly: Newly synthesized viral proteins and genomes are assembled into progeny virions within the nucleus
Maturation: Virions undergo further modifications, such as the acquisition of tegument proteins and envelopes (in Herpesviruses)
Release: Mature virions are released from the host cell through lysis or budding, ready to infect new cells
Adenoviridae: Non-enveloped dsDNA viruses that cause respiratory, gastrointestinal, and eye infections (Adenovirus)
Papillomaviridae: Small, non-enveloped dsDNA viruses that infect epithelial cells and are associated with various cancers (Human Papillomavirus)
Polyomaviridae: Small, non-enveloped dsDNA viruses that can cause tumors and multisystem diseases (JC virus, BK virus)
Poxviridae: Large, complex dsDNA viruses that replicate in the cytoplasm (Smallpox virus, Molluscum Contagiosum virus)
Parvoviridae: Small, non-enveloped ssDNA viruses that depend on helper viruses or cellular factors for replication (Parvovirus B19)
Pathogenesis and Disease
DNA viruses employ various strategies to enter, replicate, and spread within the host, leading to disease
Viral entry and replication can directly damage host cells through lysis or apoptosis
Viral proteins can interfere with host cell functions, such as cell cycle regulation, leading to uncontrolled cell growth and cancer (Papillomaviruses, Polyomaviruses)
Immune-mediated pathology: Host immune response to viral infection can cause inflammation and tissue damage
Cytokine storm: Overproduction of pro-inflammatory cytokines can lead to systemic inflammation and organ dysfunction
Latency: Some DNA viruses (Herpesviruses) can establish latent infections, persisting in the host for long periods without causing symptoms
Reactivation of latent viruses can lead to recurrent disease (cold sores, shingles)
Oncogenesis: Certain DNA viruses (Papillomaviruses, Epstein-Barr virus) can transform infected cells, leading to the development of cancers
Immune Response and Evasion
Innate immune response: Early, non-specific defense against viral infection
Type I interferons (IFN-α/β) are produced by infected cells, inducing an antiviral state in neighboring cells
Natural killer (NK) cells recognize and kill virus-infected cells
Adaptive immune response: Specific, long-lasting immunity mediated by T and B lymphocytes
CD8+ cytotoxic T cells recognize and eliminate virus-infected cells
CD4+ helper T cells support cytotoxic T cell and B cell responses
B cells produce virus-specific antibodies that neutralize viruses and mark infected cells for destruction
DNA viruses have evolved various mechanisms to evade host immune responses
Inhibition of antigen presentation: Viral proteins can interfere with MHC class I expression, preventing recognition by cytotoxic T cells (Herpesviruses)
Mimicry of host immune regulators: Viruses can produce proteins that resemble host immunomodulatory molecules, suppressing immune responses (Poxviruses)
Interference with apoptosis: Viral proteins can block apoptosis of infected cells, allowing continued viral replication (Adenoviruses)
Diagnosis and Detection
Clinical presentation: Diagnosis based on characteristic signs and symptoms of viral infection
Serological tests: Detection of virus-specific antibodies (IgM, IgG) in patient serum
Enzyme-linked immunosorbent assay (ELISA): Quantitative measurement of antibody levels
Immunofluorescence assay (IFA): Visualization of antibody binding to virus-infected cells
Viral antigen detection: Identification of viral proteins in clinical samples using antibodies
Direct fluorescent antibody (DFA) test: Fluorescently labeled antibodies bind to viral antigens in infected cells
Molecular methods: Detection of viral nucleic acids in clinical samples
Polymerase chain reaction (PCR): Amplification and detection of viral DNA sequences
Real-time PCR: Quantitative measurement of viral load
Viral culture: Isolation and growth of the virus in cell culture systems, followed by identification using immunological or molecular methods
Treatment and Prevention
Antiviral drugs: Medications that inhibit viral replication or block viral entry into host cells
Acyclovir and valacyclovir: Nucleoside analogs that inhibit Herpesvirus DNA polymerase
Cidofovir: Nucleotide analog that inhibits viral DNA polymerase in Adenoviruses and Poxviruses
Immunoglobulins: Passive immunization using preformed antibodies to neutralize viruses or modulate immune responses
Vaccines: Active immunization to prevent viral infections
Live attenuated vaccines: Weakened viral strains that induce immunity without causing disease (Varicella vaccine)
Inactivated vaccines: Killed viruses that stimulate an immune response (Hepatitis A vaccine)
Subunit vaccines: Purified viral proteins that elicit protective immunity (Hepatitis B vaccine)
Virus-like particle (VLP) vaccines: Self-assembling viral capsid proteins that mimic the structure of the virus (Human Papillomavirus vaccine)
Infection control measures: Practices to prevent the spread of viral infections
Hand hygiene, personal protective equipment (gloves, masks), and proper disinfection of surfaces
Isolation of infected individuals to minimize transmission