Infection retrovirus

Persistent viral infection is a difficult challenge for antiviral chemotherapy. Retroviruses as a class are often found to be responsible for persistent viral infections. Retroviruses are unique RNA viruses characterized by the transcription of their single-stranded RNA into the double-stranded DNA of the host cell using the viral enzyme reverse transcriptase. AIDS is an example of such a persistent and latent human viral infection. 

The viruses responsible for AIDS are human immunodeficiency virus 1 and 2 (HIV 1 and HIV 2) Both are retroviruses, meaning that their genetic material is RNA rather than DNA HI Vs require a host cell to reproduce and the hosts m humans are the T4 lymphocytes which are the cells primarily responsible for inducing the immune system to respond when provoked The HIV penetrates the cell wall of a T4 lymphocyte and deposits both its RNA and an enzyme called reverse transcriptase inside There the reverse transcriptase catalyzes the formation of a DNA strand that is complementary to the viral RNA The transcribed DNA then serves as the template from which the host lymphocyte produces copies of the virus which then leave the host to infect other T4 cells In the course of HIV reproduction the ability of the T4 lymphocyte to reproduce Itself IS compromised As the number of T4 cells decrease so does the body s ability to combat infections... 

On the other hand, EFN-a may also be involved in the activation of autoreactive T-cells as has been proposed for type I diabetes. An DFN-a inducible superantigen, encoded by the truncated envelope gene of a human endogenous retrovirus and specifically activating V 37 T-cells, has been detected in pancreatic lesions from type I diabetes patients, infiltrated by V 37 T-cells. Since IFN-a expression could be detected in pancreatic (3 cells in conceit with persistent viral infections, there is a clear link between viral infections and autoimmunity via IFN-a-stimulated superantigen expression. 

In contrast to retroviruses, proteolysis is an early event in the replication cycle of (+)-strand RNA viruses and both protease and polymerase inhibitors can be expected to halt the propagation of infectious viral particles from already infected cells. 

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Retroviruses Human T-cell leukaemia virus (HTLV-1) Spherical enveloped virus lOOnm in diameter, icosahedral cores contain two copies of linear RNA molecules and reverse transcriptase HTI.V is spread inside infected lymphocytes in blood, semen or breast milk. Most infections remain asymptomatic but after an incubation period of 10-40 years in about 2% of cases, adult T-cell leukaemia can result... 

Human immunodeficiency virus (HIV) is a retrovirus, i.e. its RNA is converted in human cells by the en me reverse transcriptase to DNA which is incorporated into the human genome and is responsible for producing new HIV particles. Zidovudine (azidothymidine, AZT Fig. 5.22F) is a stmctural analogue of thymidine (Fig. 5.22A) and is used to treat AIDS patients. Zidovudine is converted in both infected and uninfected cells to the mono-, di- and eventually triphosphate derivatives. Zidovudine triphosphate, the aetive form, is a potent inhibitor of HIV replication, being mistaken for thymidine by reverse transeriptase. Premature ehain termination of viral DNA ensues. However, AZT is relatively toxic because, as pointed out above, it is converted to the triphosphate by eellular enzymes and is thus also aetivated in uninfected cells. 

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Hanna LE, Bose JC, Nayak K, Subramanyam S, Swaminathan S. Short communication influence of active tuberculosis on chemokine and chemokine receptor expression in HIV-infected persons. AIDS Res Hum Retroviruses 2005 21(12) 997-1002. 

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