Virology Flashcards
What is a virus?
A virus is an infectious obligate intracellular parasite comprising genetic material (DNA/RNA) and is surrounded by a protein coat (capsid) and sometimes a lipid membrane (envelope).
The genome of the virus (RNA/DNA) consists (usually) of a very small number of genes. The genes must contain enough information to build new virus particles when a cells is infected.
Viral replication cycle: a general overview for viruses.
The main steps in replication are the same for all viruses. Host cell functions as a factory, providing substances, energy, and replication machinery that are essential for the synthesis of viral proteins and viral genome replication. Non-cellular processes must be encoded in the viral genome. The replication consists of 9 steps:
1: recognition
2: attachment
3: penetration
4: uncoating
5-7: transcription, synthesis of macromolecules, and replication
8: assembly
9: release
Latency: what is it? Why is an advantage for a virus?
Virus latency is generally maintained by a few viral genes that keep the viral genome silent and escape from host immune system.
Efficient establishment of latency allows the viral genome to persist despite host immune responses to many viral antigens, and other potentially adverse signals in the microenvironment.
Examples of virus: herpesviruses, retroviruses
Latency offers a relatively safe reservoir. It allows the microbe to travel with the host with the possibility of reaching new populations.
Immune-privileged niches: what is it? Why is it an advantage for a virus?
Immuno-privileged niches include the eyes, brain, testes or placenta. Besides the physical barriers present in these tissues (ex: blood-retina barrier or blood-brain barrier), immune cells found at these sites also do not function in the same manner as they do elsewhere in the body. Some viruses exploit these sites to cause persistent infections, ex: Ebola virus (infect macrophages in the epididymis in persistent infections), zika virus (detected in semen up to 6 months after infection), and rabies virus (proliferate in the CNS, avoiding the innate immune response of the host).
Concurrent infections: what is it? Can you give some examples?
Concurrent infections occur when 2 or more pathogens infect a host at the same time.
Example: HIV causes lytic and latent infection of macrophages, DCs and CD4+ T cells.
What are the strategies of viral pathogenesis? Explain some.
Stages of viral pathogenesis:
1: transmission to a susceptible host
Transmission: the virus must break through the host’s protective barriers (skin, mucous membranes).
2: establishment of primary infection
Primary infection: the virus must break through the host’s protective barriers; the virus replicates in cells that are susceptible and permissive. Often cells in the mucous membranes in the mouth, or upper respiratory or urogenital tract.
The virus can spread to secondary replication sites: via lymph, blood (viremia), or through neurons. Secondary viremia (= replication of viruses in secondary sites that once again are spread via the blood).
3: activation of the innate immune response
4: incubation period
The period between exposure to an infection and the appearance of the first symptoms. Period in which the virus replicates, but has not reacted the target tissue or caused enough damage to cause symptoms.
Short incubation period: the primary site of infection is the target tissue
Long incubation period: virus must spread to other tissues or symptoms are due to the immune response.
5: viral replication in target tissue
Replication in the target tissue gives characteristic clinical symptoms. Both the virus and the host’s immune system may cause tissue destruction and systemic effects.
Cytopathogenesis: 4 possible outcomes: non-productive infection (no replication), lytic infection (cell death), persistent infection (no cell death), or latent infection (virus present without active replication).
6 activation of the adaptive immune response
7: viral transmission
Transmission is dependent on target tissue and how stable the virion is (enveloped or naked virus). Examples: respiratory, fecal-oral, direct contact, zoonoses, blood transfusion or organ transplant, sexual contact, transmission to the fetus or newborn, genetic.
Horizontal transmission = direct between individuals (vector-transmitted, airborne, etc.)
Vertical transmission = from mother to offspring
Latrogenic transmission = via veterinarian/physician (infected needles)
Nosocomial transmission = in hospitals, drop infection, etc.
Zoonotic transmission = between other animals and humans
8: outcomes of viral infection
Two possible outcomes: elimination of virus or persistent infection.
The host usually develops antibodies to protect against recurrent infections with the same virus. The host’s immune system determines whether an infection becomes acute or persistent.
What is the tipping point of a viral disease?
The “tipping point” of a viral disease refers to a critical threshold/moment in the progression of the disease at which significant and often irreversible changes occur, leading to either rapid improvement or deterioration in the patient’s condition. This concept can be applied to individual cases or illness as well as to the dynamics of viral outbreaks within a population.
Individual level - involves the interplay between the virus’s ability to replicate and spread and the host’s immune response. Including; the viral load, immune response (overactive vs adequate response), and complications.
Population level - in the context of viral outbreak of epidemic, it refers to the stage at which the spread of the virus is either significantly curtailed or escalates rapidly. Including; the reproduction number (R0; the tipping point is reached when R0 drops below 1 = the outbreaks is likely to die out); herd immunity (vaccination); public health interventions (lockdowns, widespread testing etc.)
What factor determine the ability of a virus to cause disease and how severe the disease is?
It is dependent on viruses and host factors:
Viral factors: point of entry and infection site; inoculum size (amount of virus); and genetics (virulence factors).
Host factors: immune status/response; age, health, condition; genetics.
When the host is infected, it is the immune status and immune response that determine the outcome of the viral disease.
Pathogenesis of viral diseases: how can it be explained that airborne viruses that initially infect the respiratory tract airways of the host produce lesions in other parts of the body - ex: measles, encephalitis, lymphoid organs (immune amnesia)?
1: initial infection and replication
Entry - the airborne viruses enter the body primarily though inhalation, infecting the epithelial cells lining the respiratory tract. This is the primary site of viral entry and initial replication.
Local replication - after infecting the respiratory tract, the virus replicates locally, leading to the initial symptoms of infection (cough, sore throat, and runny nose).
2: dissemination to other tissues
Viremia - following replication in the respiratory tract, many viruses can enter the bloodstream (viremia). This systemic spread is facilitated by the breakdown of local tissue barriers, immune cell transport, or direct infection of endothelial cells lining the blood vessels.
Tissue tropism - viruses have specific tissue tropism (= they have a preference for infecting certain types of cells or tissues). This tropism is determined by the presence of specific receptors on host cells that the virus can bind to and infect. Ex: measles virus bind to SLAM (signaling lymphocytic activation molecule) receptor which is found on immune cells.
3: infection of secondary sites
Immune system involvement - measles virus infect immune cells (ex: lymphocytes), which are then transported throughout the body, including the lymphoid organs (spleen and LNs). This widespread dissemination can lead to generalized immune suppression or “immune amnesia”, where existing immunity to other pathogens is diminished.
Neurological spread - some viruses can also spread to the nervous system, either via the bloodstream or along peripheral nerves. Ex: viruses can reach the brain and cause encephalitis, either through direct infection of neural tissue or via infected immune cells crossing the blood-brain barrier.
4: systemic and organ-specific disease
Manifestation of symptoms - the infection of diverse tissues and organs leads to a wide range of symptoms, depending on the organs affected. Ex: measles cause characteristic rash, respiratory symptoms, and Koplik spots in the mouth, along with potential complications like encephalitis and pneumonia.
Immune response and inflammation - the systemic immune response to the virus, including the release of cytokines and other inflammatory mediators, can contribute to symptoms and tissue damage. In severe cases, this can lead to conditions like cytokine storm (life-threatening).
What are some of the viral structures recognized by the innate immune system?
Virus sensing in the cytosol: cells possess receptors and signaling pathways to induce type I IFN (alpha, beta, lambda) gene expression to cytosolic viral presence. Ex: the presence of dsRNA.
Virus sensing in the endosome: most viruses encounter the endocyclic pathway on their way in and out of cells. Accordingly, a subset of TLR appears to be dedicated to surveying endosomes for viral presence (nucleic acids). Those are TLR 3, TLR7, TLR8, and TLR9.
Virus sensing at the cell surface: TLR2 and TLR4 have been suggested to play a role in sensing of viruses. However, this recognition is often restricted to some components in a few virus isolates (HSV, retrovirus, RSV)
What drives a viral evolution?
Four drivers of virus evolution:
1: large numbers of progeny
2: large numbers of mutants - genetic drift
3: quasi-species effect - genetic bottleneck
Viral infections are initiated by a population of viral particles, not a single virus. The large number of progeny produced are products of selective forces inside the host. The survivors can re-infect a new host reflect the selective forces outside the host.
Survival of the fittest: a rare genome with a particular mutation may survive a selection event, and this mutation will be found in all progeny genomes.
Survival of the survivors: linked but unselected mutations will also survive. The product of selection after replication is a new population that shares only the selected mutations.
4: selection - first 3 are the raw materials for selection
How is a viral evolution constrained?
Despite many rounds of replication, mutation and selection, we can recognize the different viruses genomes by sequence analysis.
Viral populations often maintain a consensus sequence, even if the possibilities of variation are almost infinite.
The stability is maintained; extreme alterations due not survive selection; the physical nature of the viral capsid is very difficult to modify in a way that would allow the virus to survive; there is selection during host infection (a mutant to efficient will disappear quickly, and the same will happen to a mutant that does not replicate enough).
How do antiviral drugs work (in general)?
Drugs can inhibit viral replication, by affecting receptors on the outside of the host cell, or by penetrating the cell to stop viral replication.
Most antiviral agents act on viral enzymes or virus structures that are important for replication (all steps).
Why are there so few antiviral drugs?
Antiviral drugs are potentially toxic; difficult to affect the virus without affecting the cell’s machinery, because viruses use the cell’s genetic and metabolic mechanisms. And, most antiviral agents have a toxic effect on the cell at high concentrations.
Some viruses are specially challenging; difficult to propagate, no animal models (smallpox), and can be dangerous viruses (Ebola virus).
Resistance to antiviral drugs will appear while treating a patient; viruses replicate efficiently giving a “high” mutation rate and high progeny.
