Diseases caused by persistent virus infections include acquired immune deficiency syndrome (AIDS), AIDS-related complexes, chronic hepatitis, subacute sclerosing panencephalitis (chronic measles encephalitis), chronic papovavirus encephalitis (progressive multifocal leukoencephalopathy), spongioform encephalopathies (caused by prions), several herpesvirus-induced diseases, and some neoplasias. Persistent infections are characterized as those in which the virus is not cleared but remains in specific cells of infected individuals. After the initial EBV infection and replication in epithelial cells (e.g., pharynx, salivary glands), the virus persistently infects hematopoietic cells. Suppression of latent HSV, VZV and CMV reactivation has been achieved in many immunocompromised patients receiving acyclovir and/or ganciclovir treatment. Due to this mechanism, HIV can reproducibly create a latent infection. The mechanisms by which CMV replication and latency are regulated remain unclear. This results in transformation of the cell. Latent Infection: Virus remains in a cell and does not replicate, as in HSV, VZV, CMV, EBV, and HIV. Replication Cycle:.
HSV, VZV and CMV have inverted repeat sequences. Direct repeats do not allow recombination and so EBV and HHV6 have only one isoform. Once epithelial cells are infected, there is replication of the virus around the lesion and entry into the innervating neurone. More than 90 of adults have been infected with at least one of these, and a latent form of the virus remains in most people. This prevents proper folding of the MHC and therefore the MHC does not reach the cell surface. It can only work in herpes virus infected cells because, in order to be active, the drug must be changed by an enzyme (thymidine kinase) which is encoded by herpes viruses and therefore only present in cells infect with these viruses. Once acquired, CMV, as with all herpes viruses, remains present for life. Varicella -Zoster virus (VZV), Epstein Barr virus (EBV) and CMV. These are called Fc receptors and can provide a way for HIV to get into a cell that does not have CD4 molecules on its surface.
Non-structural viral proteins: expressed in infected cell but not virion particle ie. How does HSV avoid the host immune response and remain latent? Persistent infection: viral continues to replicate at very low levels e.g. HIV, HBV, CMV, EBV Mechanisms of Persistence: – antigenic variation – immune tolerance – restricted gene expression – modulation of host immune response by virus – infection of immune-privileged sites – direct infection of immune cells. The susceptibility of a particular cell to viral infection depends mainly on the presence of cellular receptors. Localized – viral replication remains localized near the site of entry e.g. skin, respiratory or the GI tract). It is thought that adequate levels of neutralizing antibodies do not persist in respiratory secretions, even though sufficient circulating antibodies are present. These latent infections include CMV, VZV, HSV, EBV, adenoviruses, measles, human papillomaviruses, JC and BK viruses. There are eight currently identified members of the human herpes virus family. Alpha-herpesviruses: HSV 1 and 2; VZV – these have a relatively short reproductive cycle, variable host range, efficiently destroy infected cells and establish latent infections primarily in sensory ganglia. Latency can be maintained in the white cells of the blood, kidneys, secretory glands and other tissues.
Thus, first clinical episode of genital herpes does not necessarily equate with acquisition of HSV in the genital tract, a fact that should be remembered in counseling couples in long-term monogamous relationships in whom one partner has a first clinically recognized case of genital herpes. When clinically apparent, symptoms remain localized to the genital region (46, 88, 167). HIV viral load increases when HSV-2 infection reactivates in HIV-infected persons (154). Viruses that cause chronic infection constitute a stable but little-recognized part of our metagenome: our virome. This decision point may be reached very early in infection for viruses that can establish a latent infection, in which case the infection is permanent regardless of the course of acute infection. Isolated in 1986 during attempts to find novel viruses in patients with lymphoproliferative diseases, HHV-6 is now recognized as a T-cell lymphotropic virus with high affinity for CD4 lymphocytes. After primary infection, HHV-6 remains latent unless the immune system is compromised, at which time the virus may reactivate. For example, in these patients, reactivation of HHV-6 has been associated with CMV reactivation and increased severity of CMV disease. In patients infected with HIV, HHV-6 infection may up-regulate HIV replication and hasten the progression toward AIDS. Viral infections remain a significant cause of morbidity and mortality following renal transplantation. Another study of patients suspected of having CMV disease did not demonstrate a correlation between the degree of viremia and the pathologic presence of virus. Post-transplant prophylaxis against reactivation of VZV and HSV is recommended to prevent severe recurrences and consists of ganciclovir in patients needing CMV prophylaxis. EBV can cause replication and clonal expansion of the B cells that serve as its primary reservoir and other cell lines as well.