Viral Pathogenesis Flashcards
Explain the effects of tissue tropism on the nature of viral disease
tissue specificity is determined by access to the tissue in which it can replicate, receptors required for virus binding and entry, expression of host genes required for virus infection and production of new progeny virus, and a relative failure of host defenses. It can lead to virus population variants among or within individuals (esp in viruses prone to replication errors)
Explain the effects of virulence on the nature of viral disease
transmission affected by site of virus rep and release as well as the relative stability of the virus particle in the environment (i.e. enveloped are most likely transmitted by close contact because they are sensitive to outside factors; non-enveloped can sustain environmental factors are transmitted by virus-associated objects/fomites and use resp or fecal/oral routes)
-most transmission is horizontal but can be vertical or germ-line associated
Explain the effects of host responses on the nature of viral disease
these factors include expression of appropriate receptors for virus entry, accessibility and permissivity (ability of cells to support virus replication) of infected cells, age of host, genetic background, immune status.
-Immune mediated = antibody mediated (immune complex disease) and cell mediated (rash, fever and malaise), autoimmunity (cross-reaction with virus) and transient immune modulation (immune suppression)
Requirements for successful initial infection:
sufficient virus, cells at site of entry that are susceptible and permissive to infection, local host defenses that are absent or initially insufficient to block infection
“sufficient virus”
free virus particles must survive environmental exposure or limit exposure between hosts, virus must be abundant enough to initiate infection (concentration, virus particles can be defective), initial infection can be quite inefficient
Viral acute infection:
high viral rep rate and production of a large # of progeny. Replication is limited by host death or host immune response. Can lead to a persistent infection if not cleared AND can be transmitted
Acute local disease: incubation periods, virus shedding and transmission, host responses, and likelihood of re-infection.
(ex. Common cold and diarrheal disease)
- Incubation period: short (1-3 days)
- Virus shedding and transmission: usually on the epithelial cells a the body surface (gut, respiratory tract, eyes). No viremia or secondary replication sites
- Host response: have short-lived immunity, primarily via secretory IgA
- Likelihood of re-infection: include viruses which have many serotypes -> common re-infections
Acute systemic disease: incubation periods, virus shedding and transmission, host responses, and likelihood of re-infection.
(ex. Measles and smallpox)
Incubation period: 10-21 days
-Virus shedding and transmission: starts in epithelium but secondary replication happens at various sites (i.e. lymphoid organs, lungs, skin) caused by viremia and systemic infection
-Host response: secretory IgA and serum IgG
-Likelihood of re-infection: lifelong immunity
Describe the expected outcome of viral infection and disease in a healthy host versus an immune compromised host, including symptoms, shedding and transmission, and length of primary infection
Immunocompromised hosts are going to be more susceptible to viral infection because they do not have adequate immune responses, therefore they will have worse symptoms and longer lengths of primary infection
Persistent
usually refers to virus infections that continue to produce new virus over a long period of time
Latent
refers to virus infection in which the virus genome is relatively silent, there is little gene transcription in most infected cells, and there is little to no disease in a healthy host for a long time, in many cases for life. Latent virus differs from dead-end infections (those caused by defective virus or which lack the ability to ever produce virus) in that they retain the ability to re-initiate transcription and replication to produce new virus. This process is referred to as reactivation or recrudescence.
Examples of the different types of viral disease
- Acute Local = Colds, diarrhea
- Acute Systemic = Smallpox, measles
- Chronic = Rubella in neonate
- Latent = VZV in nerves
- Slow/Progressive = AIDS, cancer
- aberrant disease outcomes in immunocompromised
List the potential outcomes and types of virus diseases, with the contributing factors
1) Recovery – host immune response gets rid of the virus and the host makes a full recovery fully eliminating or repressing all viruses
2) Chronic Disease – The host is unable to rid itself entirely of the virus and continues to have symptoms that may be persistent or may come and go (persistent vs latent) – The ability of a host to rid itself of the disease depends on the status of the immune system and how clever the virus is
3) Death – If the host is unable to combat the virus and the virus is allowed to replicate unchecked, the host can eventually succumb. This will usually only occur with viral infections to which the host does not have a response (novel) or to which the host cannot mount a response.
Some viruses transform =
returvirus can integrate into the host genome and activate viral or host oncogenes, other viruses may or may not integrate to cause host DNA breakage and oncogene activation or inactivation of a tumor suppressor. Finally, some virus infections (particularly persistent infections) may cause ongoing inflammation and so contribute to tumorigenesis
