SMITH, continued

HIV AND ITS EFFECTS

HIV and AIDS are often times used interchangeably. However, AIDS is caused by the human immunodeficiency virus (HIV), which affects and weakens the body’s immune system, allowing the body to develop life-threatening infections and cancers. The term AIDS, Acquired Immune Deficiency Syndrome, is used to define the most advanced stages of the HIV infection, that is, it applies to people who have encountered serious complications due to HIV (HIV Infection and AIDS, 2004).

Virus Structure

HIV is thought to contain two identical copies of single-stranded RNA, approximately 9500 nucleotides in length, which may be linked together to form a genomic RNA dimer (Human Immunodeficiency Virus: Structure and Pictures, n.d.). The two strands of RNA are associated with a nucleocapsid protein and are found within a bullet-shaped capsid along with other viral proteins, such as integrase and reverse transcriptase, which are essential for the maturation of the virus. The capsid is engulfed by a layer of matrix protein that is directly attached to the envelope of the virus. The HIV envelope is a phospholipid bilayer that was derived from the host cell as the virus budded out. Throughout the HIV envelope are peg-like structures that consist of three or four gp41 glycoproteins stems capped with three or four gp120 glycoproteins (The Structure and Life of HIV, 2004). These glycoproteins are antireceptors, that is, they are involved in the attachment and fusion of the virus to the host cell.

HIV Infection: The HIV Life Cycle

HIV is a lentivirus, which is a subgroup of retroviruses known for their latency upon infection, persistent presence in the blood of the host, infection of the nervous system, and the debilitation of the host’s immune system (Dubin, 2004). Retroviruses contain RNA as their genetic make up and the reverse transcriptase enzyme, which they use to convert their genome to DNA. HIV interacts with its host cells by binding to special receptors known as CD4 receptors that are found on white blood cells known as helper T lymphocytes or helper T cells or CD4+ cells, which play an integral role in coordinating the body’s immune system (Gandhi et al., 1999).

Furthermore, the virus may target other cells involved in the body’s immune system, such as monocytes and macrophages (The Structure and Life of HIV, 2004). In addition to binding to CD4 receptors on the host cell using its gp120 glycoproteins, interactions with co-receptors such as CCR5 or CXCR4 are needed for the virus to enter the host cell (Gandhi et al., 1999). The CCR5 co-receptor has been shown to be critically involved in the binding of the virus to the host cell, since individuals’ hemizygous for mutations in the CCR5 region are resistant to infection by HIV (Pieribone, 2002/2003). Upon binding to the receptors and co-receptors, the viral envelope fuses with the cell membrane of the host cell allowing viral penetration to occur, that is, the entry of the viral genome and viral proteins (the nucleocapsid of the virus) into the cytoplasm of the cell (Pieribone, 2002/2003). The nucleocapsid is then partially dissolved to release the viral RNA and viral proteins. The viral genome is then transcribed to form double-stranded DNA using the reverse transcriptase enzyme, which was released into the host’s cytoplasm during penetration. The reverse transcriptase enzyme uses nucleotides, the building blocks of DNA, found in the cell’s cytoplasm to make the double-stranded DNA (Pieribone, 2002/2003). During this process of transcription various mutations occur in the viral genome (HIV, n.d.). This process of transcription of the viral genome from RNA to DNA is only possible because of the presence of the reverse transcriptase enzyme. Upon transcription, the double-stranded DNA travels to the nucleus of the cell where it integrates itself into the cell’s genome using the integrase enzyme, which was also deposited into the cell during penetration. The genetic make-up of the cell is now known as a provirus, that is, it is retroviral DNA that has been integrated into the human genome (Provirus, n.d.).

The virus now latently infects the host, that is, it remains dormant in the host cell’s genome until the cell becomes activated. The latency period of the life cycle of HIV, which varies, allows the virus to replicate and multiply when the genome of the host cell is replicated and multiplied. Once the cell becomes activated, the virus uses the machinery of the cell to produce proteins, which are compiled to make new virons, virus particles. This process is implemented when the viral DNA is transcribed back to two strands of RNA, which are transported out of the nucleus. One strand is called a messenger RNA and the other strand represents the viral genome that is packed into new viral particles. Viral messenger RNAs, like all other messenger RNAs, are composed of regions known as codons that “code” for various proteins. In the case of HIV, the messenger RNA codes for proteins critical to the maturation of the virus: protease, integrase and reverse transcriptase (The Structure and Life Cycle of HIV, 2004). Proteases are enzymes that cleave long strands of proteins, known as polyproteins, to produce functional proteins. Hence, the viral protease cleaves the viral proteins to produce functional products, which assemble at the cell membrane of the host cell (Gelman, 2004). The final stage of the life cycle of the virus results in the budding of the viron out of the host cell. This occurs when functional products attach to the cell membrane to allow the formation of the nucleocaspid. The nucleocaspid then merges with the cell membrane and buds off the cells. Ultimately, the infected host helper T cells die and the body’s immune system weakens (Ghandhi et al., 1999).

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