Viral Genetics and Pathogenesis Flashcards
Mutation
- Change in one or a few nucleotides
- Causes subtle changes in a viral antigen
- Allows a virus to escape pre–existing antibody or primed cytotoxic T– lymphocytes (CTL)
Examples of Mutation
•Antigenic drift in influenza A virus
-Point mutations accumulate in influenza virus two envelope proteins, hemagglutinin (H) and neuraminidase (N), resulting in changes in the antigenic structure of the virus particle or virions
•Genetic variability in retroviruses
-Retroviruses (HIV) show high rates of variation because of the error-prone reverse transcriptase enzyme that converts RNA genome into DNA genome in infected cells
Recombination
- Exchange of genetic information with a closely related co–infected virus
- Both DNA and RNA viruses exhibit recombination
Example of Recombination
•antigenic shift of influenza A viruses due to either recombination or reassortment of segments of viral RNA.
-Leads to new viral strains, which have resulted in pandemics
•Recombination is also seen in HIV infection
Complementation
- One of two infecting viruses has mutation that results in a non-functional protein (protein X)
- The native virus complements the mutated virus by making a functional protein (protein X) that provides function to both viruses
- Complemented virus (genome mutated) when infects cells will not make progeny viruses because the genome is still defective
Phenotype Mixing
- Mixing of two viruses A and B
- Generation of a hybrid virus with genome of A and outer surface protein of B
- Infection of new cells:
- Virus B surface protein determines the tropism – binds to the receptor on host cell
- However, the progeny viruses made will be of type A virus (both genome and surface protein)
Viral Pathogenesis
- Viral pathogenesis is the method by which viruses produce disease in a host
- Complex and dynamic interactions between the virus and host
- Viruses cause disease:
- Breach of barriers; physical and protective
- Evade local tissue and immune defenses
- Spread in the body
- Destroy cells directly or via bystander immune and inflammatory responses
Stages of Viral Pathogenesis
- Transmission and entry
- Spread
- Tropism
- Virulence
- Host factors
- Host defense
Stages of Viral Pathogenesis - Entry
Stages of Viral Pathogenesis - Spread in the Host
Stages of Viral Pathogenesis - Tropism
Stages of Viral Pathogenesis - Molecular and Genetic Determinants of Virulence
Stages of Viral Pathogenesis - Selected Mechanisms of Viral Virulence and Cytopathogenicity
Stages of Viral Pathogenesis - Transmission of Viral Infection
•Route of transmission
Stages of Viral Pathogenesis - Host Factors
•Viral infections depend on both viral and host factors
Viral Transformation
•Many DNA viruses and some retroviruses can convert normal cultured cells into abnormal cells called tumors (malignant or benign), and the process is known as viral transformation.
Properties of Malignant Tumors:
- cell morphology altered
- fail to grow in organized patterns found for normal cells
- grow to a much higher cell densities than normal cells
- lower nutritional requirements than normal cell
- grow indefinitely in cell culture
Malignant Transformation
- The process that converts normal cells into abnormal cells caused by a viral infection and cells possess the properties of malignant cells is called malignant transformation.
- All known DNA animal viruses with the exception of parvoviruses are capable of causing aberrant cell proliferation under some conditions.
- Viral transformation is the result of integration into the chromosome and continual expression of one or more viral or cellular genes .
- Some papillomavirus and herpesvirus are also found as extrachromosomal DNA.
