7.3.6B: Productive Life Cycle with Possible Latency
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- Ying Liu
- City College of San Francisco
State the major difference between the productive life cycle of animal viruses and the latent life cycle.
Define provirus.
Name 3 herpes viruses that may have a latent cycle, state in what cell types they become latent, and name the diseases each cause.
Some animal viruses, such as the herpes viruses and a group of viruses known as the retroviruses, are able to remain latent within infected host cells for long periods of time without replicating or causing harm. Some of these viruses remain latent within the cytoplasm of the host cell while others are able to insert or integrate their DNA into the host cell's chromosomes. When the viral DNA is incorporated into the host cell's DNA, it is called a provirus.
In many instances, viral latency, as well as viral persistence, is thought to be due to a process called RNA interference (RNAi) where small non-coding regulatory RNAs (ncRNAs) such as microRNAs (miRNAs) regulate gene expression. Certain viruses that infect humans are able to establish persistent infection by using their own miRNAs and/or miRNAs produced by their human host.
For example, viral and/or host miRNAs may bind to certain viral messenger RNA ( mRNA ) molecules and block translation of viral proteins required for rapid viral replication, or they may bind to the mRNA of human genes that produce proteins used in viral replication. The resulting low viral levels may then minimize immune responses against that virus. In addition, these miRNAs may directly affect host immune defenses by turning off the production of antiviral cytokines or by blocking apoptosis of infected host cells. Examples include the herpesviruses , retroviruses , and anelloviruses .
Herpes viruses, for example, are often latent in some cell types but productive in others. Herpes viruses include herpes simplex type 1 (HSV-1) which usually causes fever blisters or oral herpes, herpes simplex type 2 (HSV-2) which usually causes genital herpes, Epstein-Barr virus (EBV) which causes infectious mononucleosis and plays a role in certain cancers, varicella-zoster virus (VZV) which causes chickenpox and shingles, and cytomegalovirus (CMV) which causes a variety of infections in immunosuppressed persons and is also a leading cause of birth defects.
For more on HSV and CMV, see the AIDS Pathology Tutorial at the University of Utah.
Herpesviruses use both host and viral miRNAs to switch between the productive life cycle in infected epithelial cells whereby large numbers of viruses are produced and the infected host cells are killed (as in the case of fever blisters) and the persistent latent state in nerve cells where low levels of viruses are produced and the infected host cells are not killed by apoptosis.
With EBV, the virus is productive in epithelial cells but latent in B-lymphocytes.
In the case of HSV-1, HSV-2, and VZV, primary infection causes the virus to replicate within epithelial cells. However, some of the viruses enter and migrate down neurons where they become latent in the body of sensory neurons. Subsequent activation of the latently infected neurons by a variety of extracellular stimuli enables the viruses to migrate back up the nerve cell and replicate again in the epithelial cells. With EBV, the virus is productive in epithelial cells but latent in B-lymphocytes.
- Scanning electron micrograph of HSV ; courtesy of Dennis Kunkel's Microscopy .
In the case of HIV, the viral genome eventually becomes a provirus. After integration, the HIV proviral DNA can exist in either a latent or productive state, which is determined by genetic factors of the viral strain, the type of cell infected, and the production of specific host cell proteins.
The majority of the proviral DNA is integrated into the chromosomes of activated T4-lymphocytes. These generally comprise between 93% and 95% of infected cells and are productively infected, not latently infected. However, a small percentage of HIV-infected memory T4-lymphocytes persists in a resting state because of a latent provirus. Subsequent activation of the host cell by extracellular stimuli, however, causes the needed proteins to be made and the virus again replicates via the productive life cycle. These memory T4-lymphocytes, along with infected monocytes, macrophages, and dendritic cells, provide stable reservoirs of HIV capable of escaping host defenses and antiretroviral chemotherapy.
In the next section we will now look at the life cycle of HIV.
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