Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jul;5(7):e1000523.
doi: 10.1371/journal.ppat.1000523. Epub 2009 Jul 31.

Anatomy of viral persistence

Michael B A Oldstone  1
Affiliations

Anatomy of viral persistence

Michael B A Oldstone. PLoS Pathog. 2009 Jul.
No abstract available

PubMed Disclaimer

Conflict of interest statement

The author has declared that no competing interests exist.

Figures

Figure 1
Figure 1. Cartoon of the initiation of an uncontrolled persistent virus infection or a controlled acute virus infection in immunocompetent adults.
Dendritic cells (DC) present viral peptide/MHC complexes to activate T cells. There is an initial expansion phase following infections that lead to either clearance of the virus or virus persistence. For virus clearance, following the acute infection positive immune regulators (IL-2, IFN-γ, TNF, etc.) are generated that expand the effector virus-specific T cell pool, resulting in elimination of virally infected cells, termination of the infection, and resultant development of immune memory. By contrast, with viruses that persist there is a decreased expansion, and in some cases deletion, of virus-specific T cells. Remaining T cells become exhausted or hyporesponsive and are defective in the release of positive immune regulators and hence are unable to terminate the virus infection. The cause is the virus' induction of negative regulators of the immune response, i.e., IL-10 and PD-L1, and the cure is the blockade of such negative regulators with appropriate antibodies (see –[14]).
Figure 2
Figure 2. The scenario of virus induction of negative regulators leading to T cell hyporesponsiveness sprung from experimental analysis of LCMV infection in its natural murine host using inoculation of parental LCMV Armstrong strain 53B or its variant, LCMV Cl 13.
The 10.7-kb genome of these viruses differs by only six nucleotides that code for three amino acids. One amino acid located in the viral spike protein GP-1 at aa 260 (Leu Cl 13/Phe ARM 53b) is responsible for high affinity binding (2.5 logs higher affinity for Cl 13 over ARM 53b) for the LCMV receptor alpha-dystroglycan, which is located in the immune system, preferentially on DCs (see [32],[33]). A second important mutation is in the viral polymerase at aa 1079 (Leu Cl 13/Gln ARM 53b) and is associated with enhanced transcription and replication of LCMV Cl 13. Recent studies have also implicated infection of the fibroblastic reticular cells in lymphoid organs as contributing to the persistent infection (see [34]). Figure 2 shows this using a whole body section of a mouse. The tissue section was placed on a membrane and stained with a riboprobe to LCMV at 30 days after initiation of LCMV infection with either LCMV Cl 13 or LCMV ARM 53b. The presence of viral nucleic acids in mice receiving Cl 13 correlates directly with high titers of virus carried in the sera (PFU/ml) at 30 days post-infection and the lack of a CTL response observed 7 days after initiation of infection. By comparison, mice receiving LCMV ARM 53b at 30 days post-infection fail to display viral nucleic acid sequences or virus in their sera, as virus has been successfully purged. Further, mice infected with LCMV ARM 53b generate a robust CTL response 7 days following virus infection.
See this image and copyright information in PMC

References

    1. Biron C, Sen GC. Innate response to viral infections. In: Knipe D, Howley P, editors. Fields virology. Fifth edition. Philadelphia: Lippincott Williams & Wilkins; pp. 249–278.
    1. Braciale TJ, Hahn YS, Burton DR. The adoptive immune response to viruses. In: Knipe D, Howley P, editors. Fields virology. Fifth edition. Philadelphia: Lippincott Williams & Wilkins; pp. 279–326.
    1. Zuniga EI, Liou LY, Mack L, Mendoza M, Oldstone MBA. Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections. Cell Host Microbe. 2008;4:374–386. - PMC - PubMed
    1. Joly E, Mucke L, Oldstone MBA. Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science. 1991;253:1283–1285. - PubMed
    1. Joly E, Oldstone MBA. Neuronal cells are deficient in loading peptides onto MHC class I molecules. Neuron. 1992;8:1185–1190. - PubMed

Publication types