Monday, September 23, 2019

Discuss the regulation of gene expression in HIV and the life cycle, Essay

Discuss the regulation of gene expression in HIV and the life cycle, and comment on the importance of these in the success - Essay Example Memory helper cells are differentially infected by the virus. The virus binds to the target cell using interactions between viral surface proteins (gp120) and cell surface proteins. The CD4 antigen, and the CXCR4 and CCR5 co-receptors on the host cell membrane are crucial in mediating viral entry into the cell. The interaction allows the viral and cellular membranes to fuse, so that the viral contents, including RNA and viral enzymes, enter the host cell. The viral capsid then uncoats and disassembles to release the 2 viral RNA strands, which are used to make complementary DNA by the viral enzyme reverse transcriptase. The virus cDNA is transported to the nucleus, where the viral integrase enzyme incorporates viral DNA into the host DNA, forming the provirus. The viral DNA genome remains latent in the cell for many years, as long as the T cell is quescent. The duration of latency is indefinite and varies based on the genetic makeup of the individual. When the T cell becomes activated by cytokines to carry out the immune response, the HIV provirus also becomes activated and starts transcription, leading to the formation of new viral particles (Moore and Stevenson, 2000). Regulation of gene expression of HIV The human immunodeficiency virus (HIV) targets immune cells, specifically T helper cells, macrophages and dendritic cells. Upon entering the host immune cell, the virus RNA undergoes reverse transcription to form complementary DNA, which is then incorporated into the host genome. The viral DNA genome remains latent in the cell for many years. When the T cell is activated by cytokines to carry out the immune response, the HIV provirus also becomes activated and starts transcription, leading to the formation of new viral particles. Specifically, cytokines and antigens induce activation of NF-kB, which is a transcription factor that goes to the T cell nucleus and up-regulates the synthesis of pro-inflammatory proteins. The incorporated HIV genome also contains a site that can receive NF-kB and in response activate the gene promoter. Thus, the regulation of expression of HIV genes depends at least in part, on the activity state of the infected T cell, and transcription of HIV genes is regulated by cellular transcription factors (Robbin and Cotran, 2009). The genome of HIV contains codes for at least nine viral proteins. The structural proteins include Gag, Pol, and Env. The accessory proteins are Vpu, Vpr, Vif, and Nef. The regulatory proteinsare Tat and Rev, and they control the replication of the virus (Hope and Trono, 2000).The early genes are Tat, Rev, and Nef, and the rest are expressed late. The Tat protein is a transcriptional activator necessary for HIV replication. It promotes the elongation phase of HIV’s transcription, so that full-length, functional transcripts of the genome are produced. Rev is an RNA binding protein that acts post-transcriptionally to induce the transition from the early to the late, cytopathic phase of HIV gene expression (Cullen, 1991). It facilitates the export of unspliced and incompletely spliced viral RNAs from the nucleus to the cytoplasm, which permits the production of viral late genes so that all the proteins for the full virion can be transcribed. How gene expression regulation and life cycle contribute to the success of HIV as a pathogen HIV-1 as a pathogen is found all over the world today, while HIV-2 is restricted to

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