3.1 DNA and RNA viral genomes
4 min read•august 1, 2024
Viral genomes come in two flavors: DNA and RNA. Each type has unique features that affect how viruses replicate, evolve, and interact with their hosts. Understanding these differences is key to grasping viral behavior and developing strategies to combat them.
DNA viruses tend to have larger, more stable genomes that replicate in the nucleus. RNA viruses, on the other hand, have smaller, more mutation-prone genomes that usually replicate in the cytoplasm. These distinctions shape viral life cycles and impact how they evade host defenses.
DNA vs RNA Genomes
Molecular Composition and Structure
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- DNA viral genomes consist of deoxyribonucleic acid while RNA viral genomes contain ribonucleic acid resulting in fundamental differences in their chemical structure and properties
- DNA viral genomes can be single-stranded or double-stranded, linear or circular while RNA viral genomes are typically single-stranded but can also be double-stranded in some cases (rotaviruses)
- The sugar component in DNA viral genomes involves deoxyribose whereas RNA viral genomes contain ribose affecting the overall stability and flexibility of the genetic material
- DNA viral genomes utilize thymine as one of the four nucleotide bases while RNA viral genomes replace thymine with uracil
- Molecular weight and size of DNA viral genomes are generally larger than RNA viral genomes with some exceptions (mimivirus)
- DNA genomes range from a few thousand base pairs to over a million base pairs
- RNA genomes typically range from a few thousand to tens of thousands of bases
Genome Organization and Complexity
- DNA viruses like herpesviruses have complex genomes with multiple genes and regulatory elements while RNA viruses often have more compact genomes with overlapping reading frames
- RNA viral genomes can be positive-sense, negative-sense, or ambisense each requiring different replication strategies
- Positive-sense RNA genomes act as mRNA (hepatitis C virus)
- Negative-sense RNA genomes require complementary RNA synthesis (influenza virus)
- Ambisense RNA genomes contain both positive and negative-sense regions (arenaviruses)
- Many RNA viral genomes possess unique structures facilitating and replication
- Cap analogs mimic host mRNA 5' caps (flaviviruses)
- Internal ribosome entry sites (IRES) allow cap-independent translation (picornaviruses)
- Genome-linked proteins (VPg) act as primers for RNA synthesis (poliovirus)
- Some DNA and RNA viral genomes exhibit segmentation where genetic material divides into multiple distinct molecules
- Influenza viruses (RNA) have 8 segments
- Some bacteriophages (DNA) have segmented genomes (φ6 phage)
- Certain DNA and RNA viral genomes contain repetitive sequences or inverted terminal repeats playing crucial roles in replication and packaging
- Adenoviruses (DNA) have inverted terminal repeats for replication initiation
- Bunyaviruses (RNA) have complementary terminal sequences for genome circularization
Implications of Genome Type
Replication Strategies and Cellular Localization
- DNA viruses typically replicate in the host cell nucleus utilizing host cell machinery for while most RNA viruses replicate in the cytoplasm using virus-encoded RNA-dependent RNA polymerases
- Genome type influences the viral replication cycle
- DNA viruses often follow a DNA-to-RNA-to-protein pathway (herpes simplex virus)
- RNA viruses may directly produce proteins from genomic RNA (picornaviruses) or require an intermediate step (retroviruses)
- RNA viral genomes particularly those of retroviruses can integrate into the host genome through reverse transcription potentially leading to long-term persistence and altered host gene expression (HIV)
Host Interactions and Immune Responses
- Genome type affects virus susceptibility to host antiviral responses with RNA viruses often triggering different innate immune pathways compared to DNA viruses
- RNA viruses activate RIG-I-like receptors (RLRs) (influenza virus)
- DNA viruses stimulate cyclic GMP-AMP synthase (cGAS) (herpes simplex virus)
- Complexity and size of viral genomes influence their ability to encode proteins modulating host cell processes and immune responses
- Larger DNA viruses generally have more diverse arsenals of immunomodulatory proteins (poxviruses)
- RNA viruses often encode multifunctional proteins to maximize coding capacity (flaviviruses)
- Genome type impacts virus ability to undergo recombination and reassortment which are important mechanisms for viral evolution and emergence of new strains
- Influenza viruses (RNA) undergo frequent reassortment leading to
- Coronaviruses (RNA) exhibit high rates of recombination contributing to cross-species transmission
Stability and Mutation Rates
Genome Stability and Mutation Frequency
- DNA viral genomes are generally more stable than RNA viral genomes due to inherent chemical stability of DNA and presence of proofreading mechanisms in many DNA polymerases
- RNA viral genomes have higher mutation rates typically to mutations per nucleotide per replication cycle compared to DNA viral genomes with rates around to mutations per nucleotide per replication cycle
- Higher mutation rates of RNA viruses contribute to their rapid evolution and ability to escape host immune responses but also increase likelihood of deleterious mutations
- DNA viruses often employ host cell DNA repair mechanisms to maintain genome integrity while RNA viruses lack access to these systems contributing to their higher mutation rates
- Mismatch repair corrects DNA replication errors in herpesviruses
- Base excision repair removes damaged bases in poxviruses
Factors Influencing Mutation Rates
- Error-prone nature of RNA-dependent RNA polymerases which lack proofreading activity serves as a major factor in high mutation rates observed in RNA viruses
- Concept of a cloud of closely related viral variants appears more pronounced in RNA virus populations due to their higher mutation rates affecting their adaptability and pathogenesis
- HIV exists as a diverse population of variants within a single host
- Hepatitis C virus quasispecies contribute to treatment resistance
- Stability differences between DNA and RNA viral genomes influence their persistence in the environment and ability to maintain infectivity outside of host cells
- DNA viruses like smallpox can remain infectious in scabs for extended periods
- RNA viruses such as influenza are generally less stable outside the host
Key Terms to Review (18)
Antigenic Shift: Antigenic shift is a major change in the antigenic structure of a virus, often resulting from the reassortment of genetic material between different viral strains. This process can lead to the emergence of new viral variants that evade the immune response, which is particularly important in the context of RNA viruses, especially those with segmented genomes.
Attachment: Attachment refers to the initial binding of a virus to a host cell, a crucial first step in the viral infection process. This process is facilitated by specific interactions between viral proteins and host cell receptors, which determine the virus's ability to infect and replicate within the host.
Capsid: A capsid is the protein shell of a virus that encases and protects its genetic material. This structure is crucial for the stability of the virus outside a host cell and plays an essential role in the viral life cycle, including attachment to host cells and delivery of the viral genome. Capsids can vary in shape and size, influencing how viruses interact with their environments and how they are classified.
Cytopathic effect: Cytopathic effect (CPE) refers to the observable structural changes in host cells that result from viral infection, which can lead to cell damage or death. Understanding CPE is crucial as it connects the virus's genetic material and replication processes to the broader consequences of viral infections in different host tissues and their impact on health.
Double-stranded DNA: Double-stranded DNA (dsDNA) is a molecular structure formed by two strands of nucleotides wound around each other in a double helix, making it the primary genetic material in many organisms, including most viruses. This configuration allows for stability and the precise replication and transcription processes necessary for genetic information storage and expression.
Envelope: An envelope is a lipid bilayer that surrounds some viruses, providing an additional protective layer beyond the viral capsid. This membrane, derived from the host cell's membrane during viral replication, plays a crucial role in virus entry into host cells and evasion of the host immune response. The presence of an envelope can influence how a virus interacts with its environment and its ability to cause infection.
Frederick Twort: Frederick Twort was a British bacteriologist known for his discovery of bacteriophages, viruses that infect bacteria, in the early 20th century. His work laid the foundation for understanding the role of these viral entities in bacterial infections and opened new avenues for research on viral genomes and phage therapy, particularly related to DNA and RNA viral structures.
Herpesviridae: Herpesviridae is a large family of viruses known as herpesviruses that can infect humans and animals, characterized by their ability to establish lifelong latency in host cells. This family is significant for its diverse members, which include various human pathogens that can cause diseases ranging from mild to severe, and it plays an important role in understanding viral behavior, transmission, and pathogenesis.
Louis Pasteur: Louis Pasteur was a French microbiologist and chemist renowned for his groundbreaking discoveries in the field of microbiology and the development of vaccines. His work laid the foundation for understanding the role of microbes in disease, which significantly impacted the study of viruses, vaccine development, and public health strategies.
Lysogenic cycle: The lysogenic cycle is a method of viral reproduction in which the viral genome integrates into the host cell's DNA, allowing the virus to replicate along with the host cell without immediately causing cell death. This cycle enables the virus to persist in a dormant state, becoming a part of the host's genetic material and can later switch to the lytic cycle, where it actively produces new viruses and destroys the host cell.
Lytic Cycle: The lytic cycle is a viral replication process in which a virus infects a host cell, hijacks the cell's machinery to produce new viral particles, and ultimately leads to the destruction of the host cell. This cycle results in the release of newly formed virions, which can go on to infect additional cells, making it a crucial aspect of viral propagation.
Penetration: Penetration refers to the process by which a virus enters a host cell after the initial attachment. This step is crucial for viral infection and can involve various mechanisms, including direct fusion with the host cell membrane or endocytosis. Understanding penetration is key to grasping how viruses exploit host cellular machinery to replicate and propagate.
Picornavirus: Picornaviruses are a family of small, single-stranded RNA viruses known for their role in various human and animal diseases. These viruses have non-enveloped capsids and are typically 22-30 nanometers in diameter. Picornaviruses are significant because they include well-known pathogens such as poliovirus and rhinovirus, and their RNA genomes can directly serve as mRNA for protein synthesis upon infection of a host cell.
Quasispecies: Quasispecies refers to a group of related viral genomes that exist within a host due to high mutation rates during viral replication. This genetic diversity allows viruses to adapt quickly to selective pressures, such as the immune response or antiviral treatments, impacting their evolution, replication mechanisms, and interaction with host cells.
Single-stranded RNA: Single-stranded RNA (ssRNA) is a type of nucleic acid that consists of a single strand of ribonucleic acid, playing a crucial role in the genetic material of many viruses. This structure allows ssRNA viruses to have diverse genome organization and replication strategies, which are essential for their life cycle and ability to infect host cells. The simplicity of ssRNA enables rapid mutation rates, contributing to the evolution and adaptability of these viruses.
Transcription: Transcription is the process by which the genetic information encoded in DNA is copied into RNA. This critical step is essential for the expression of genes, as it allows the synthesis of messenger RNA (mRNA) that carries the genetic code from DNA to the ribosomes for protein production. In the context of viral genomes, transcription plays a significant role in determining how viral genes are expressed and regulated within a host cell, influencing the life cycle and pathogenicity of viruses.
Translation: Translation is the biological process in which the information encoded in messenger RNA (mRNA) is used to synthesize proteins. This process involves decoding the mRNA sequence into a specific sequence of amino acids, which are the building blocks of proteins. Understanding translation is essential, as it connects viral genetic information to the functional proteins that enable viruses to replicate and interact with host cells.
Viral tropism: Viral tropism refers to the preference of a virus to infect specific types of cells or tissues in a host organism. This selectivity is influenced by factors such as the presence of specific receptors on host cells, the viral genome, and the interplay between viral proteins and host cellular mechanisms, ultimately determining the pathogenesis of viral infections.