HIV 1959 - NOW

Over the last few decades a particular pandemic virus has taken over the world's population creating confusion and distress. This paper reviews literature from 1983 at the point when the popularity of the disease arises until the present date year 2007. in order to understand the socio-biological effect of the disease in our scientific history , the methods used to fight the virus, and the challenges that this represent to the public health at the present time. The importation retrieved displays the historical background of the virus its molecular composition, and the actual methods of detection.

Introduction

The Human immunodeficiency virus (HIV) is a virus belonging to the family Retoviridae . This are enveloped viruses processing RNA Genome, and replicate via a DNA intermediate, this virus relay on the enzyme Reverse transcriptase to perform the reverse transcription of it genome from RNA to DNA , which can then be integrate into the host genome with and integrase enzyme . the virus then replicates as part of the cell. From a biochemical stand point reverse transcriptase HIV-1 (RNA Dependent DNA polymerase) transcribes the single Stranded DNA in the Host cells. After the virus infects the genome it uses the cell resources to replicate itself am propagate around the organism.

In the early 80s a strange disease affected homosexual communities in unites, and heterosexual individuals in Sweden and Haiti, this was called the gay cancer locally this include manifestations of pneumocytis pneumonia (lung infection that occurs primarily in people with weakened immune systems--especially people who are HIV-positive. The disease agent is an organism whose biological classification is still uncertain. Pneumocystis carinii was originally thought to be a one-celled organism (a protozoan), but more recent research suggests that it is a fungus. )() at the same time as we talk about AIDS being twenty five years old, in reality it is understood that the pathology has been in the world o far longer.

In 1959, a male living Africa died of an unexplained illness, years later, after analyzing several plasma samples obtained from this subject, was established that he in fact died from complications associated to an HIV infection. In 1984, Institute Pasteur of France revealed the structure of the isolated virus, what they called the HIV virus, but it was not until a year later a US scholar, Dr. Robert Gallo established that HIV was the source of AIDS. Subsequent to this discovery, the first test for HIV was accepted in 1985. Over the next numerous years medications to fight the virus were created as well as medicines to prevent infections that flourish when the immune system is damaged by HIV and AIDS. By the end of 1987, there were 71,000 established cases of AIDS, consequential in over 40,000 deaths.

Among of the best recognized publications on the history of HIV is 1987's book "And the Band Played On", by Randy Shilts. Shilts contend that Ronald Reagan's government dragged its feet in managing with the crisis owed by homophobia, while the gay population observed early on reports and public health actions with resultant to distrust, as a result allowing the illness to extend, and hundreds of thousands of individuals to unnecessarily die. This resulted in the development of ACT-UP, the AIDS Coalition to Unleash Power by Larry Kramer.

This work popularized the mistaken belief that the disease was introduced by a gay flight attendant named Gaëtan Dugas, referred to as "Patient Zero". However, subsequent research has revealed that there were cases of AIDS much earlier than initially known. HIV-infected blood samples have been found from as early as 1959 in Africa (see HIV main entry), and HIV has been shown to have caused the death of a sexually active St. Louis boy in 1969.

Shilts also fine points in the fact that despite recommendations from the Centers for Disease Control, the Red Cross and other non-profit blood banking organizations refused to ban bisexual and gay men from donating blood in an effort to keep the blood bank industry from suffering shortages. As a result, tens of thousands of hemophiliacs and transfusion recipients were infected and died.

It has been theorized that a sequence of inoculations against hepatitis that were performed in the gay population of San Francisco were contaminated with HIV. even though there was a elevated association linking recipients of that vaccination and initial cases of AIDS, this theory has never been confirmed. HIV, hepatitis B, and hepatitis C are bloodborne pathology with exceptionally comparable modes of transmission , and individuals at risk for one are at risk for the others. Activists and critics of current AIDS policies claim that another unnecessary obstacle to the attack on the disease was the academic elitism of "celebrity" scientists. Robert Gallo, an American scientist who was one of many to endeavor to figure out if there was some kind of new virus in the people who were affected by the disease, became entangled in a legal battle with French scientist Luc Montagnier. Gallo, too, appeared hung up on the potential connection between the virus causing AIDS and HTLV, a retrovirus that he had worked with previously.

Critics claim that because some scientists (and biological research companies) wanted glory and fame (and lucrative patent rights), research progress was delayed and more people needlessly died. Eventually, after meeting, the French scientists and Gallo agreed to "share" the discovery of HIV. Publicity campaigns were started in attempts to counter the often vitriolic and homophobic perception of AIDS as a "gay plague." In particular this included the Ryan White case, red ribbon campaigns, celebrity dinners, the 1993 film version of And the Band Played On, sex education programs in schools, and television advertisements. Announcements by various celebrities that they had contracted HIV (including actor Rock Hudson, basketball star Magic Johnson, and tennis player Arthur Ashe) were significant in making the general public aware of the dangers of the disease to people of all sexual orientations.

The virus

HIV is different in structure from other retroviruses. It is about 120 nm in diameter (120 billionths of a meter; around 60 times smaller than a red blood cell, also known as Heritocytes ) and roughly spherical.It is composed of two copies of positive single-stranded RNA that codes for the virus's nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein. The single-stranded RNA is tightly bound to nucleocapsid proteins, and enzymes needed for the development of the virion such as reverse transcriptase, proteases, ribonuclease and integrase. A matrix composed of the viral protein surrounds the capsid ensuring the integrity of the virion particle. This is, in turn, surrounded by the viral envelope which is composed of two layers of fatty molecules called phospholipids taken from the membrane of a human cell when a newly formed virus particle buds from the cell. Embedded in the viral envelope are proteins from the host cell and about 70 copies of a complex HIV protein that protrudes through the surface of the virus particle. This protein, known as Env, consists of a cap made of three molecules called glycoprotein (gp) 120, and a stem consisting of three molecules that anchor the structure into the viral envelope.

This glycoprotein complex enables the virus to attach to and fuse with target cells to initiate the infectious cycle. Both these surface proteins, especially gp120, have been considered as targets of future treatments or vaccines against HIV. Of the nine genes that are encoded within the RNA genome, three of these genes, gag, pol, and env, contain information needed to make the structural proteins for new virus particles. env, for example, codes for a protein called gp160 that is broken down by a viral enzyme to form gp120 and gp41. The six remaining genes, tat, rev, nef, vif, vpr, and vpu (or vpx in the case of HIV-2), are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus (replicate), or cause disease. The protein encoded by nef, for instance, appears necessary for the virus to replicate efficiently, and the vpu-encoded protein influences the release of new virus particles from infected cells. The ends of each strand of HIV RNA contain an RNA sequence called the long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell.

Introduction

Since the initial description of the human immunodeficiency virus type I (HIV-1) in 1983 (Barre-Sonoussi 1983, Gallo 1983) and HIV-2 in 1986 (Clavel 1986), these two viruses have been identified for almost 20 years as the primary cause of the acquired immunodeficiency syndrome (AIDS). As HIV-1 is the major cause of AIDS in the world today, our discussion will be primarily limited to HIV-1 infection. Worldwide, the number of HIV-1 infected persons exceeds 40 million, the majority of whom live in the developing countries of Sub-Saharan Africa, Asia and South America.

The introduction of protease inhibitors and non-nucleotide reverse transcriptase inhibitors (NNRTIs) to antiretroviral treatment regimens in 1995 began the era of highly active antiretroviral therapy (HAART), and resulted in dramatic improvements in the mortality and morbidity of HIV disease, as determined by a decreased incidence of opportunistic infections, tumors, and deaths.

Despite all the therapeutic advantages achieved during the last decade, including the development of HAART, once an individual has become infected, eradication of the virus still remains impossible. In addition, new problems relating to the short- and long-term toxicity of drug treatments and the occurrence of resistance mutations in both circulating and transmitted viruses are emerging. In most countries in South East Asia and Africa, the incidence and prevalence of HIV-1 infection continues to increase and surpass that of Europe and North America. However, due to the high costs of drug regimens and the lack of a healthcare infrastructure in these developing countries, the widespread use of HAART is currently still difficult. The further course of the HIV-1 pandemic, therefore, mainly depends on how and to what degree the developing countries with a high HIV-1 prevalence are able to take advantage of the medical progress achieved in Europe and North America, and whether an effective prophylactic vaccine becomes available in the near future.

An understanding of the immunopathogenesis of HIV-1 infection is a major prerequisite for rationally improving therapeutic strategies, developing immunotherapeutics and prophylactic vaccines. As in other virus infections, the individual course of HIV-1 infection depends on both host and viral factors.

The course of infection with HIV-1 in HIV-infected humans may vary dramatically, even if the primary infections arose from the same source (Liu 1997). In some individuals, with a long-term non-progressive HIV-1 infection (i.e., lack of decline in CD4+ T-cell counts, or chronic infection for at least 7 years without the development of AIDS), a defective virion was identified (Kirchhoff 1995). Thus, infection with a defective virus, or one that has a poor capacity to replicate, may prolong the clinical course of HIV-1 infection. However, in most individuals, HIV-1 infection is characterized by a replication-competent virus with a high daily turnover of virions.

Host factors may also determine whether or not an HIV-1-infected individual rapidly develops clinically overt immunodeficiency, or whether this individual belongs to the group of long-term non-progressors, who represent about 5 % of all infected patients. The identification and characterization of host factors contributing to the course of HIV infection, including immunological defense mechanisms and genetic factors, will be crucial for our understanding of the immunopathogenesis of HIV infection and for the development of immunotherapeutic and prophylactic strategies.

Sexual transmission of HIV-1 requires the crossing of mucosal tissue, and the precise mechanism of viral transmission across this barrier is poorly understood. The virus can enter through capture by intra-epithelial dendritic cells (DC), which extend processes into the lumenal surface to sample contents and to trap pathogens (see figure below). Alternatively, HIV-1 crosses at places of thinning, breaches or lesions caused by hormones or other (sexually transmitted) diseases. In the latter case, the virus has access to subepithelial dermal DC.

DC are professional antigen presenting cells that sample the environment at sites of pathogen entry. Sentinel immature DC develop into mature effector DC upon activation by microorganisms, and migrate to the draining lymph nodes where they stimulate naïve Th cells. HIV-1 has been proposed to make use of this migratory process, being captured by the DC and delivered to the lymph node where the virus is transmitted to CD4+ T cells. The lymph node then becomes the principal site of virus production.

DC can capture HIV through several receptors, of which DC-SIGN is the best studied example. After capture, the virus dissociates from DC-SIGN and resides in an unidentified non-lysosomal compartment (box A, figure below). After T cell encounter, HIV is recruited to the site of T cell interaction. This so-called 'infectious synapse' depends on strong cell-cell adhesion mediated by ICAM-1-LFA-1 interaction (box B). The precise composition of the synapse is largely unknown

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Diagnosis

ELISA is the Enzyme-Linked Immunoadsorbent Assay. It's a sensitive immunoassay used to detect a specific protein - for example antibodies to HIV borne in a sample of blood.There are a few methods for performing an ELISA. Here is one common one, and the one relevant to detecting HIV antibodies:

Put a specific antigen protein (i.e. prepared HIV protein) in a plastic container. The protein molecules bind (adsorb) to the plastic by hydrophobic or other attraction.

Add the serum sample from the patient. If the patient serum contains HIV antibodies, these will attach to the HIV antigens already present.

Wash the container gently, so that all the unbound components of the patient serum are washed away.

Add an antibody which is raised to recognise the human antibody, and of which each molecule is covalently linked with a molecule of an enzyme such as alkaline phosphatase or peroxidase - any enzyme which can catalyse a chromogenic reaction.

Wash the container gently, so that any unbound test antibody from the previous step is washed away.

Add the reagents which are the inputs to the chromogenic reaction. These reagents will only react in the presence of the enzyme - that is, where our test antibodies have bound to the plastic container via the antibody/antigen complexThe colour produced in the container is an indication of the amount of antibody found.

Normally the ELISA is performed in a multi-welled container, and a positive result comes when the amount of wells showing the appropriate colour change is a certain proportion.False positives can occur - for example antibodies induced by a recent flu jab can cause a positive result - and so although ELISA's an important diagnostic test for HIV, it should be followed up with a Western blot test.

The Western blot tests for antibodies to a particular protein(s). In HIV diagnosis a set of HIV proteins are laid out on a nitrocellulose film and then a sample of blood serum from a patient is added to the film. If the serum contains any antibodies to HIV proteins then the antibodies will latch on at the appropriate position on the film.

As in the ELISA test, we then need to be able to see whether antibodies have attached - and just as in the ELISA test, we do that by washing the film gently and adding an enzyme which will attach to antibodies present and which can catalyse a chromogenic reaction.

Again we wash the strip, and then add the ingredients for that chromogenic reaction. Where antibody has bound, we see colour produced.

There are different standards for interpreting the Western blot. The US Multicenter AIDS Cohort Study 1983-1992 suggests that three weak bands or any strong band indicates a positive result. Other standards require that there must be at least one band representing antibodies to envelope protein before a positive result can be reported.

The HIV virus has been for many years a challenge to the medical scientific community, today a vaccine is being tested to prevent the infection , but this still in its initial development , and I might take too long before it can be used in the general population . in the mean time this pathology still spreading around our population ,While we attempt to understand more intrinsically the molecular components of the virus to create more effective ways to attack it. This ill ness have over taken the worlds population physical and social health and had brought with it death and confusion among masses. There still a lot to be done by our scholars to overcome the challenge that this pathology represents but with the right education an prevention we will be able to combat this disease with success eventually.

Works cited

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• Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for AIDS. Science 1983, 220: 868-71.

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• Annabel Kanabus & Sarah Allen. Updated by Bonita de Boer (2007). The Origins of HIV & the First Cases of AIDS. AVERT (an international HIV and AIDS charity based in the UK). Retrieved on 2007-02-28.