The Hiv 1 Life Cycle

The virus fuses with the cell’s plasma membrane. The capsid proteins are removed, releasing the viral proteins and RNA. Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. Reverse transcriptase catalyzes the synthesis of a second DNA strand complementary to the first. The double-stranded DNA is incorporated as a provirus into the cell’s DNA. Proviral genes are transcribed into RNA molecules, which serve as genomes for the next viral generation and as mRNAs for translation into viral proteins. The viral proteins include capsid proteins and reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER). Vesicles transport the glycoproteins from the ER to the cell’s plasma membrane. Capsids are assembled around viral genomes and reverse transcriptase molecules. New viruses bud off from the host cell.

CD4 is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. HIV infects cells of the immune system called T lymphocytes (T cells) and macrophages. HIV has an envelope and contains two copies of single-stranded RNA as the genome. Within the viral capsid are important viral enzymes called reverse transcriptase, integrase, and protease. The HIV virus has a spike protein that is called gp120, and the host cell receptor is CD4+. HIV belongs to a class of viruses called retroviruses. Retroviruses are RNA viruses, and to replicate or reproduce, they must make a DNA copy of their RNA through transcription and translation. It is the DNA genes that allow the

J.’s CMP results are unremarkable and the flu was ruled out with a negative flu test. The CBC results show leukopenia and thrombocytopenia as evidenced by

b. HIV is an incurable disease that relies on coreceptors to initiate host cell interaction and proliferates by utilizing the host cell’s own machinery to reproduce new virus. We will more deeply explore the mechanism in which HIV virions infiltrate and deceive our host cell. In addition, we will discuss current treatment and research that are in the process of finding a highly coveted cure.

Recent studies suggested that CD4 domain specific monoclonal antibody such as mAb (15A7) and Ibalizumab have a great revolution in HIV-1 treatment area. The majority of previous mentioned treatments constitute to either restore the immune response or decline the plasma vireamia, however, this type of treatment is more likely to interfere with the HIV-1 structure. Before explaining how this category of drugs works, it is necessary to clarify the reaction between HIV-1 glycoproteins and CD4. Once the virus enters the body, HIV-1 envelope glycoprotein (gp120) attaches to a cellular CD4 receptor. As CD4/gp120 is formed, it allows gp120 to attache to chemokine receptor-5 (CCR5) or CX chemokine receptor-4 (CXCR4) allowing gp41, another viral envelope molecule, to insert into the target cell membrane leading to fusion the viral envelope and cellular membrane (Christopher et al., 2010). Ibalizumab is CD4 domain-2 monoclonal antibody using as an effective treatment to enhance the CD4 counts. In a study which set out to determine the antiviral efficacy of Ibalizumab on HIV-1 positive patients not on (ART), (Christopher et al., 2010) found that the CD4 counts increase after one day of drug initiation even before the viral load decline. This suggested that the rise of CD4 counts is possibly due to redistribution of CD4 cells from lymphoid tissues rather than regeneration of these cells. Notably, niegher

gp41 (envelope antigen), are highly immunogenic, the antibody responses vary according to the virus load and the immune competence of the host. The antigenicity of these various components provides a means for detection of antibody, the basis for most HIV testing.[35] Accessory genes carried by HIV include tat, rev, nef, vif, vpr, and vpu (for HIV-1) or vpx (for HIV-2). The rev gene encodes for a regulatory protein which switches the processing of viral RNA transcripts to a pattern that predominates with established infection, leading to production of viral structural and enzymatic proteins. The long terminal repeat (LTR) serves as a promoter of transcription.[22,30,32,33]

The synthesis of the viral glycoproteins HA & NA starts in the cytoplasm and later these growing polypeptide chains are transported to the endoplasmic reticulum where the proteins are modified and assembled into trimers and tetramers ( Samji T.,2009).These proteins are then transported through the Golgi apparatus and the trans-Golgi network to the plasma membrane of the cell where they inserted finally. The synthesis and folding of viral core proteins occur entirely in the cytoplasm. NP and the RNA polymerase components interact with newly synthesized viral RNA to form RNPs. The M1 protein forms interaction with the C-terminal domains of HA and NA protein on the cell plasma membrane. The newly formed RNPs interact with the M1 protein. This interaction also stops re-entry of RNPs inside the nucleus of the cell. After attachment of RNPs to M1protein where it act as a bridge on the inner half of the cell plasma membranes, in a process of budding, the new virus particles are assembled . The progeny virions bud off from the host cell. (Shi etal.,2014).As soon as budding takes place, the new virions are still attached to the cell surface through interaction of the HA with sialic acid moieties on cellular glycoproteins or glycolipids. The

HIV (Human Immunodeficiency Virus) puts its own genome directly into a host cell during the time of infection (Ebina et al, 2013). This can lead to AIDS (acquired immunodeficiency syndrome) if it is left untreated. AIDS is caused by a retrovirus. HIV can remain dormant for years once its DNA is in the host cell (Fessenden, 2015). HIV infects

AIDS (Acquired immunodeficiency syndrome) is disease caused HIV (human immunodeficiency viruses). This research paper describes the evolution and origination of HIV and AIDS. There are two types of HIVs. These are called HIV-1 and HIV-2. HIVs result multiple cross species transmission from SIV (simian immunodeficiency viruses) that is viruses that infects primates. HIV-1 comes from SIV from chimpanzees whereas HIV-2 comes from sooty mangabeys. HIV-1 has four sub groups these includes M, N, O, and P. Each of groups has resulted from independent cross-species transmission event. Group M is the most virulent, and it is the first to be discovered. HIV-2 has groups that ranges from A to H. SIV are infecting West Africa primates. This fact is based on the first pandemic HIV-1 has emerged in colonial West African, and most researchers have sampled primates from this region only. Newly emerged SIVs are resulted from multiple cross species transmission and recombination. The cross species transmission occurs from non-humans to humans through eating bushmeat. The cross transmission influenced by host restriction factors, but HIVs were able to pass this barriers. Most SIV are non-pathogenic to the host; however, there is some evidence that some are pathogenic to their host. The age of the virus determined by using molecular clock method. Other studies have estimated the evolutionary timescale with same age as

Human immunodeficiency virus is a retrovirus that affects the T cells specifically to the immune system. In spite of, lowering the immunity of humans and claiming the lives of many people around world. H.I.V replication is a multi- stage process and every step is necessary to complete its process. (“T Cell”) In step one, the entry of the virus requires certain receptors from the host cell such as a CD4. In addition, these receptors are composed of two glycoproteins that are embedded in the viral envelope. (“Kestens, P.”) By approaching the target, the cells of a gp120 connects to the CD4 receptors and the transmembrane gp41 is capable of transferring its information into the cell membrane. Uniquely, this process creates a pathway for the virus to fuse with the host cell. When it enters the cell it breaks open and releasing two viral RNA strands and three essential replication enzymes.

Ebola, and AIDS, Acquired Immunodeficiency Syndrome, are both dangerous zoonotic diseases that originated in Sub-Saharan Africa. AIDS, the result of HIV, human immunodeficiency virus, has been an ongoing pandemic for decades. Meanwhile, the first Ebola case was recognized in the 1976 and has incurred severe sporadic outbreaks but has been controlled (Rajak, 2015). While both rapidly mutating RNA viruses, several key factors have allowed AIDS, to become a worldwide pandemic while Ebola has been controlled at present (Calmy, 2015). Understanding the evolution, life history, and the socio-economic factors that affect the proliferation of each disease allows us to understand how they arose when they did and why Ebola is controlled and AIDS isn’t.

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

HIV-1 integrase is one of the key enzymes required for the successful replication of HIV-1 and is often a common therapeutic target to help treat HIV-1 infections. Integrase is a

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).