Hiv Virus Research Paper

The positive effects of viruses are less obvious. Viruses can function as vaccines for similar but more harmful diseases, be scientifically interesting and broaden our understanding of biology, or have applications in genetic engineering as transfer vectors (“Gene transfer vector”, 1999.) This is because of the way that viruses infect cells and replicate. Viruses consist of a protein coat around a nucleic acid, which may be DNA or RNA- not a combination of the two. The protein coat functions to protect the nucleic acid and attach to and recognize a host cell. Shapes of viruses are helical, polyhedral, enveloped, and complex (Starr, C., et al, 2004). Enveloped viruses are an exception to the protein coat structure, in that they have a lipid bilayer surrounding. Viruses are 20 to 400 nanometers in diameter (Elert, G., 2004). Independent of a host cell, a virus is called a virion. When just the nucleic acid is present, it is called a viroid.

In the past four decades, human immunodeficiency virus (HIV) has been discovered, developed into an international epidemic, and

Nucleoside reverse transcriptase inhibitors: It stops the HIV virus from making copies by interfering with a critical step during its life cycle.

HIV is very popular in America HIV belongs to a group of retroviruses called lentiviruses. The genome of retroviruses is made of RNA. And every virus has two single chains of RNA, for replication, the virus needs a main cell, and the RNA must first be transcribed into DNA, which can be done with the enzyme reverse transcriptase. HIV infects mainly the CD4+ lymphocytes. It also to a lesser degree monocytes, macrophages, and dendritic cells. Once infected, the cell turns into an hiv-replicating cell and loses its function in the human immune system. HIV is a ball-shaped virus. It has two single strands of RNA for its genome. The RNA is made to carry the genetic information that passed on when new hiv particles are produced. This is different from a normal cell and it uses DNA to carry its genetic information.

The HIV-1 life cycle is complicated and its period and result is contingent upon the target cell type and cell activation. In the beginning, HIV-1 enters the cells without producing instant damage but by entering the cells it can provoke intracellular signal cascades, which may assist the progress of viral replication. The external glycoprotein (gp120) and the transmembrane protein (gp141) are two molecules on the HIV-1 envelope that form the spikes on the virion’s surface. In the entry process, gp120 first attaches to the CD4+ receptor and then attaches to the cell membrane. Interactions between the virus and chemokine co-receptors will cause permanent conformational changes. The fusion event will occur within minutes by pore formation and it will discharge the viral core into the cell cytoplasm. Once the core dismantles, the viral genome will be reverse transcribed into DNA by the virus’ own reverse transcriptase enzyme. Viral variants may develop at the time of this process because reverse transcriptase is error prone. During the midpoint of infection, both the viral protein integrase and the host DNA repair enzymes will inject the viral genome into the active domain of the host’s chromosomal DNA. Lens epithelium-derived growth factor (LEDGF/p75) is an integrase binding host factor that assists the progress of integration, which converts the cell into a virus producer. In the late stages, production of viral particles will need both host driven and virus driven

The juxtapositional co-receptor attachment to the host membrane encourages the GP41 protein to initiate fusion by collapsing into a hairpin loop structure bringing the two membranes in close proximity. The virus then injects the contents of the virion including machinery enzymes and the RNA genome into the host cell where a dsDNA molecule is made and integrated into the host. The reverse transcription process has a high mutation rate because the viral reverse transcriptase enzyme is unable to detect or repair any mistakes as it forms the dsDNA. After the new dsDNA molecule is made it is transported to the nucleus of the host and integrated into the host genome. The HIV genome will either remain in a lysogenic state within the host or if actively stimulated new HIV viruses will be constructed and released to infect neighboring cells.

The HIV-1 virion is approximately 120 nm in diameter, roughly spherical, and is composed of two copies of a single stranded positive sense RNA enclosed by a capsid (24). The HIV-1 genome is less than 10 kb and encodes for more than nine different gene products. It encodes for 3 major structural protein genes: gag (group-specific antigen), pol (DNA polymerase), and env (Envelope), which code for major structural proteins and essential enzymes. Gag generates the mature Gag protein matrix (MA or p17), capsid (CA or p24), nucleocapsid (NC or p7), and p6, which encompass proteins for the basic infrastructure of the virus such as the inner core of the viral particle (25). Pol encodes for reverse transcriptase (RT), which enables the virus to reproduce, integrase (IN), which is necessary to integrate the viral double stranded DNA into the host genome, RNAse H, and HIV protease, which are all encapsulated in the core of the inner particle formed by the viral capsid protein p24 (25). Env encodes for glycoproteins of the outer membrane such as outer gp120 (which enables the virus to attach and fuse to cells of the host), and transmembrane gp41 that anchors the glycoprotein complex to the surface of the virion (25). Between the core and the envelope is the HIV matrix proteins which are composed of the viral protein p17 (23). HIV-1 also encodes for proteins with important regulatory elements (tat (Trans-Activator of Transcription) and rev

Thesis statement: HIV infected cells destroys the bodies’ white blood cells, affecting ones immune system and in turn altering patient’s lifestyle choices and circumstances.

At that point, the following stride for the HIV disease is getting its hereditary material into the host 's cell 's DNA. Ignatavicius (2013) states that "HIV fits in with a group of infections called retroviruses; its hereditary material is single-stranded RNA" (p.359). The hereditary material of the human cell is twofold stranded DNA. With the goal HIV should contaminate and assume control over a human cell, the hereditary material must be the same. HIV conquers this issue by bringing a chemical called reverse transcriptase, which changes over RNA to DNA. This makes HIV have the same hereditary material as the human cell DNA. This finishes the disease of the CD4 T-cell. HIV debilitates the safe framework by expelling some CD4 T-cells from flow. It makes that range a HIV manufacturing plant where it can keep on duplicating its infection.

A virus is a tiny obligate intracellular parasite which has its RNA or DNA genome surrounded by a protein protective coat1. A virus may be viewed as a movable genetic element1. For integration and propagation of a virus, the virus will have to depend on the host cell which will serve as complex metabolic and biosynthetic machinery1. A mature virus is often referred to as a virion which exerts its effect by transferring its genomic DNA or RNA to the host cell and then undergoes replication so that its genome can be expressed in the host cell1.

This binding induces a conformational change in gp120, which exposes its binding site to its cellular co-receptors. CCR5 and CXCR4, two receptors first identified as CC- and CXC- chemokine receptors, respectively, are the most reported co-receptors for HIV infection. Other chemokine receptors, including CCR2, CCR3, and CX3CR1 have also been reported to be utilized by HIV as co-receptors (He et al., 1997; Garin et al., 2003; Puissant et al., 2003). The Interaction between gp120 and these co-receptors triggers further conformational change and the insertion of HIV-1 gp41 into the host cell membrane, which initiates the fusion of the membranes and eventually leads to entry of the virus genome and proteins. Once the host cell is infected, the viral reverse transcriptase makes viral DNA using its RNA genome template. The newly synthesized viral DNA binds to the viral protein integrase and some host proteins to form the pre-integration complex, which then translocate to the nucleus, integrate to the host genome, and form the provirus. Infected cells can either be latent, or actively transcribe and produce virus and viral proteins such as Tat, gp120, Nef and Vpr.

Human Immunodeficiency Virus (HIV) is a retrovirus responsible for the acquisition of HIV infection which leads to the development of acquired immunodeficiency syndrome (AIDS). HIV targets cells that are part of the human immune system such as CD4+ T cells, macrophages and dendritic cells which results in the levels of these cells falling dangerously low as they are exterminated via different mechanisms. Such mechanisms typically involve the induction of signaling cascades that result in 'self-killing' protocols being executed by the cell, as well as becoming targets for direct killing of other cytotoxic cells in the immune system. As HIV is a lentivirus it contains two single-stranded, positive sense, RNA molecules each coding nine viral

Resistant viruses can recognize, bind to and utilize the maraviroc/CCR5 complex for entry. Amino acid mutations in gp120 alters the way the protein interacts with CCR5. These modifications cause resistant viruses to be heavily reliant on the CCR5 N-terminus for entry (Roche et al 2015). There are two mutations on maraviroc resistant R5 HIV. These mutations replace Ala316 and Ile323 with Thr316 and Val323 on the V3 loop of the wild type HIV-1 CCR5 tropic strain. The Val323 mutation in the V3 loop of gp120 changes the secondary structure of the V3 loop making the loop less rigid and permits altered interactions with the N-terminus that allows for HIV-1 entry. A loss of beta sheets in the stem of the V3 loop occurs with the presence of the Val323 mutation. In addition, the smaller valine side chain may reduce steric interference and permit closer interaction with the residues on the N-terminus of CCR5. Thus, the Val323 mutation makes the V3 loop more fluid, allowing for closer interactions with the N-terminal of CCR5. In the presence of Maraviroc, HIV-1 resistant strains become considerably dependent on the interaction with N-terminal residues Try3, Tyr10, Tyr13, Tyr14, Tyr15, Glu 18, and Asp11.

HIV is a retrovirus and it differs from normal RNA viruses because they contain an enzyme known as reverse transcriptase. This enzyme transcribes an RNA template into DNA, opposite of what normally occurs in a replication cycle (Reece et al., 2014). There is viral DNA produced through this method; which then invades the nucleus of the cell and combines itself into the DNA of a chromosome. This differs from the typical process, as it is a multistep process; contrary to the single step mechanism of incorporating mRNA into host cells to produce viral proteins (MCRH). HIV is a retrovirus and has a much more complex viral replication, compared to the

Proteolytic processing of the Gag polyprotein results mature HIV-1 structural proteins: p17 matrix (MA), p24 capsid (CA), p7 nucleocapsid (NC), p6 domains, and two spacer peptides, SP1 and SP2. Each of these HIV-1 structural proteins play a crucial role in the HIV-1 retroviral replication cycle. MA is responsible for targeting Gag to the plasma membrane and promoting the incorporation of viral envelop glycoproteins into the forming virions; CA drives Gag multimerization during assembly to form the Gag lattice that encapsidates the viral RNA genome; NC recruits the viral RNA genome into the virions; and the p6 domain recruits the endosomal sorting complex required for transport (ESCRT) apparatus that catalyzes the membrane fission step responsible for the budding off of new virions from the infected cell (Freed, 2015). In HIV-1 pathogenesis, HIV-1 matrix protein p17 participates in several processes, including RNA targeting to the plasma membrane, incorporation of the envelope into virions, and particle assembly. Furthermore, p17, acting as a viral cytokine, can act on reactivated T-cells, promoting viral proliferation (Florentini et al, 2006).