Latent infection

Varicella-zoster virus is a member of the Herpesviridae femily. The viral contagion is transmitted via aerosolized water droplets or close physical contact with infected lesions. The primary infection results in varicella or chickenpox. The varicella infection can have potentially devastating ocular sequelae the most common is anterior uveitis followed by SPK. After the primary infection, latent infection occurs in multiple ganglia throughout the body. Herpes zoster is the resultant reactivation of the latent varicella-zoster virus and most often occurs in elderly and immunocompromised patients. Factors such as physical and emotional trauma, immunosuppressive medications, irradiation, cancer, tuberculosis, malaria, and syphilis are known to reactivate the virus. 

For the pathogenesis of multiple sklerosis, autoimmune T-lymphocy tes play a predominant role, which are directed against components of the neural myelin sheath. T-lymphocy tes by secreting cytokines such as interferon y maintain the chronic inflammation which destructs the myelin sheath. Also cytotoxic T-lymphocytes may participate directly. The cause of multiple sklerosis is unknown. Significantly increased antibody titers against several vitusses, mostly the measles virus, point to a (latent) virus infection initiating the disease. 

COPD is a chronic inflammatory disease that results from prolonged and repeated inhalation of particles and gases, chronic (or latent) infection or an interaction of these factors. In many cases, the inflammation persists even when the exposure (in most cases smoking) is stopped. Prominent among the infiltrating leukocytes are neutrophils, CD8+ lymphocytes (Co-receptor for the T-cell receptor. CD8+ is specific for the class IMHC protein. It is expressed on the surface of cytotoxic T-cells and natural killer cells.) and CD68+ monocytic cells (A lysosomal antigen. All cells that rich in... 

Acute infection with Hetpes simplex viruses (HSV) results in painful rashes on skin and mucous membranes. HSV-1 mainly causes cold sores around the mouth (hetpes labialis) or eyes (keratitis), whereas infection by HSV-2 mostly results in sores in the genital or anal area. Less frequently, HSV also causes severe infections in newborns or potentially fatal encephalitis. HSV remains latent and can be reactivated by stress, suppression of the immune system or other infections. 

The best example of using this knowledge in drug discovery is the identification of Prostratin. While working in Samoa to identify plants with potential chemotherapeutic properties, Dr. Paul Cox documented the use of Homalanthus nutans for the treatment of hepatitis [16]. Surprisingly, when extracts of this plant were incidentally examined for anti-HIV properties, the extract appeared effective for treatment of HIV [17]. Eventually, this compound was shown to be effective at activating the latently infected T-cell pool [18]. Importantly, this population of cells is a principal reason for HIV persistence [19]. 

In 1995, HlV-1 latency was first documented in HIV-1-infected patients when ex vivo T cell cultures were found to contain a subpopulation of cells that produced infectious virions when stimulated with T cell activators (Chun et al. 1995 Finzi et al. 1997). Latently infected T cells are rare, to the order of one in a million resting... 

Hematopoietic progenitor cells Bailey et al. (2006) Reseeding of a viral variant from a rare infection event of a few progenitor cells raises the possibility that the bone marrow compartment may be a source of latent provirus... 

Chun TW, Engel D, Berrey MM, Shea T, Corey L, Fauci AS (1998) Early establishment of a pool of latently infected, resting CD4(-I-) T cells during primary HIV-1 infection. Proc Natl Acad... 

Ikeda K, Nagano K, Kawakami K (1993) Possible imphcations of Spl-induced bending of DNA on synergistic activation of transcription. Gene 136(l-2) 341-343 Ishida T, Hamano A, Koiwa T, Watanabe T (2006) 5 long terminal repeat (LTR)-selective methy-lation of latently infected HIV-1 provirus that is demethylated by reactivation signals. Retrovirology 3 69... 

McElrath MJ, Steinman RM, Cohn ZA (1991) Latent HlV-1 infection in enriched populations of blood monocytes and T cells from seropositive patients. J Clin Invest 87(l) 27-30... 

Survival of the infected cell unchanged, except that it now carries the virus in a latent state. 

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