The Regulation of Gene Expression in HIV and the Life Cycle - Essay Example

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 quiescent. 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 proteins Tat and Rev, and 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 

West Africa. HIV emerged as a pathogen in the twentieth century, only a few decades ago, and likely crossed over from chimpanzees. Its persistence and ability to evade and destroy the immune system lies in several factors.

How does the life cycle contribute to the success of HIV as a pathogen?

In the first stage of the life cycle, HIV uses specialized surface proteins that allow the virus particle to carry out specific and effective interaction with the target cell (the CD4 positive cells), allowing entry of the virus into the cell where it can survive intracellularly. Also, the virus’s replication is dependent on the activation and proliferation of the host cell. This is achieved when the induction of cellular activation proteins takes place, which also activates the HIV genome and initiates the synthesis of viral proteins. This makes viral replication more effective (Ferguson, Rojo, von Lindern and O'Brien, 2002).

How does gene expression regulation contribute to the success of HIV as a pathogen?

The HIV-1 virus shows significant genetic variability during viral replication, owing to the poor loyalty and lack of proofreading of the viral reverse transcriptase. This genetic variability allows many non-lethal mutations to occur that allow the virus to escape immune mechanisms and also prevents the development of an effective vaccine. Also, as the virus contains two RNA strands and the two strands can undergo recombination during replication, this magnifies the amount of genetic variation that can take place. The integration of viral DNA into the host genome, and the capability to stay latent, allows the virus to persist within the body and protects it from the immune system, while slowly destroying T cells that get activated, thus chipping away at the immune system. The viral accessory genes, such as Nef, have also been associated with increased virulence. Among a range of effects, the Nef protein inhibits cell apoptosis, presumably to promote the persistence of viral replication in the cell. It also triggers apoptosis in cells neighbouring the virus-infected cell, which may contribute significantly to the virus’s destructive effect on the immune system. However, the exact mechanisms of all the accessory proteins are not yet well defined.