HIV (HUMAN IMMUNODEFECIENCY VIRUS):INTRODUCTION:

The acquired immune defficiency syndrome (AIDS) caused by infection with the retrovirus known as Human Immunodeficiency Virus (HIV), was first described in 1981.Notlong afterwards , reports began to appear of neurological complications including an unusual encephalopathy, in effected patients. HIV attacks the body's immune system. Normally, the immune system produces white blood cells and antibodies that attack viruses and bacteria. The infection fighting cells are called T-cell lymphocytes. Months to years after a person is infected with HIV, the virus destroys all the T-cell lymphocytes. This disables the immune system to defend the body against diseases and tumors. Various infections will be able to develop, these opportunistic infections take advantage of the body's weakened immune system. These infection which normally won't cause severe or fatal health problems will eventually cause the death of the HIV patient.

HIV:HIV stands for Human Immunodeficiency Virus. Like all viruses, HIV cannot grow or reproduce on its own. In order to make new copies of itself it must infect the cells of a living organism.

HIV AND ITS TARGET:

HIV is an RNA virus that belong to the cless of viruses called retroviruses.The viral RNA and an importana enzyme called reverse transcriptase are enclosed within a protein coat (capsid), forming the core of the virus. The core is surrounded by an envelop, composed of a double layer of lipid molecules, that was acquired from the cell membrane of the infected cell when the virus budded from the cell.The target of the HIV virus is the CD4 protein present on the cell membranes of helper T lymphocytes,as well as om moncytes, macrophages and similar macrophage-like cells in the skin, lymph nodes and within the central nervous system. The CD4 protein functions as a receptor for the virus, to which the virus attaches. When the virus binds to the cell, the virus envelope fuses with the cell membrane and the virus enters the cell.Once inside the cell, the virus makes a DNA copy of its own RNA genetic material by means of its reverse transcriptase enzyme and the DNA copy is inserted into the genetic material of the infected cell, a process assisted by another

viral enzyme called HIV integrase and the viral genes direct the synthesis and the assembly of more virus.The final stages of virus production requires a viral enzyme called HIV protease, which cuts and assembles the virus protein into small segments that surrounded the viral RNA, forming the infectious virus particles that bud from the infected cells. The newly formed virus particles attack other susceptible cells within the lymphoid tissues throughout the body, where the virus replicates (proliferates) and releases more virus particles to infect still more susceptible cells.Helper T lyphocytes, which are primary targets for the virus, are damaged and many are killed. Monocytes, however, which are also attacked, are quite resistant and survive, but the virus continues to replicate within the monocytse, releasing virus particles theat infect other cells. In addition, the monocytes function as vehicles to transport the virus throughout the body and into the nervous system to infect the brain.

STRUCTURE OF HIV:

This picture shows the structure of Human Immunodeficiency Virus.The outer shell of the virus is known as the Viral envelope.Embedded in the viral envelope es a complex protein known as env which consists of an outer protuding cap glycoprotein (gp) 120, and a stem gp14.Within the viral envelpoe is an HIV protein called p17 (matrix) and within this is the viral core or capsid which is made up of another viral protein p24 (core antigen). The integrated form of HIV-1, also known as the provirus, is approximately 9.8 kilobases in length. The genes of HIV are located in the central region of the proviral DNA and encode at least nine proteins.

GAS PROTEIN:
The gag gene gives rise to the 55 kilodalton Gag precursor protein, also called p55, which is expressed from the unspliced viral mRNA. After budding, p55 is cleaved by the virally encoded protease during the process of viral maturation into four smaller proteins designated MA (matrix [p17]), CA (capsid [p24]), NC (nucleocapsid [p9]), and p6.

GAG-POL PRECURSOR:
The viral protease, integrase, RNAse H, and reverse transcriptase are always expressed within the context of a Gag-Pol fusion protein. During viral maturation, the virally encoded protease cleaves the Pol

polypeptide away from Gag and further digests it to separate the protease (p10), RT (p50), RNAse H (p15), and integrase (p31) activities.

HIV-1 PROTEASE:
The HIV-1 protease is an aspartyl protease that acts as a dimer. Protease activity is required for cleavage of the Gag and Gag-Pol polyprotein precursors during virion maturation.

REVERSE TRANSCRIPTASE:
The pol gene encodes reverse transcriptase. During the process of reverse transcription, the polymerase makes a double stranded DNA copy of the dimer of single stranded genomic RNA present in the virion.

INTEGRASE:
The integrase protein mediates the insertion of the HIV proviral DNA into the genomic DNA of an infected cell.

ENVELOPE PROTEINS:
The 160 kD Env (gp160) is expressed from singly spliced mRNA. A cellular protease cleaves gp160 to generate gp41 and gp120. Gp41 contains the transmembrane domain of Env, while gp120 is located on the surface of the infected cell and of the virion through non covalent interactions with gp41. Env exists as a multimer, most likely a trimer, on the surface of the cell of the virion.Interactions between HIV and the virion receptor, CD4, are mediated through specific domains of gp120.

REGULATOR PROTEINS :
Tat:
Tat is a transcriptional transactivator that is essential for HIV-1 replication.Tat is an RNA binding protein, unlike conventional transcription factors that interact with DNA.The mechanism of Tat function remains controversial. From some studies, it appears that Tat acts principally to promote the elongation phase of HIV-1 transcription,other studies indicate that Tat may be involved in the phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II.

Rev:
Rev is a 13-kD sequence-specific RNA binding protein. Rev acts to induce the transition from the early to the late phase of HIV gene expression.

ACCESSORY PROTEIN:

Nef:
Nef has been shown to have multiple activities, including the down regulation of the cell surface expression of CD4, the perturbation of T-cell activation, and the stimulation of HIV infectivity.

Vpr:
The Vpr protein is incorporated into viral particles. Vpr plays a role in the ability of HIV to infect non dividing cells by facilitating the nuclear localization of the preintegration complex.Vpr can also block cell division.

Vpu:
HIV-2 does not contain vpu, but instead harbors another gene, vpx. The 16-kD Vpu polypeptide is an integral membrane phosphoprotein that is primarily localized in the internal membranes of the cell.In HIV infected cells, complexes are formed between the viral receptor, CD4, and the viral envelope protein in the endoplasmic reticulum causing the trapping of both proteins to within this compartment. The formation of intracellular Env-CD4 complexes thus interferes with virion assembly. Vpu liberates the viral envelope by triggering the degradation of CD4 molecules complexed with Env.Vpu also increases the release of HIV from the surface of an infected cell.

Vif:
Vif is a 23-kD polypeptide that is essential for the replication of HIV in peripheral blood lymphocytes, macrophages, and certain cell lines.

What does HIV look like?

In this computer generated image, the large object is a human CD4+ white blood cell, and the spots on its surface and the spiky blue objects in the foreground represent HIV particles. Outside of a human cell, HIV exists as roughly spherical particles (sometimes called virions). The surface of each particle is studded with lots of little spikes. An HIV particle is around 100-150 billionths of a metre in diameter. That's about the same as: 0.1 microns 4 millionths of an inch one twentieth of the length of an E. coli bacterium one seventieth of the diameter of a human CD4+ white blood cell. Unlike most bacteria, HIV particles are much too small to be seen through an ordinary microscope. However they can be seen clearly with an electron microscope. HIV particles surround themselves with a coat of fatty material known

as the viral envelope (or membrane). Projecting from this are around 72 little spikes, which are formed from the proteins gp120 and gp41. Just below the viral envelope is a layer called the matrix, which is made from the protein p17. The proteins gp120 and gp41 together make up the spikes that project from HIV particles, while p17 forms the matrix and p24 forms the core. The viral core (or capsid) is usually bullet-shaped and is made from the protein p24. Inside the core are three enzymes required for HIV replication called reverse transcriptase, integrase and protease. Also held within the core is HIV's genetic material, which consists of two identical strands of RNA.

What is RNA?
HIV belongs to a special class of viruses called retroviruses. Within this class, HIV is placed in the subgroup of lentiviruses. Other lentiviruses include SIV, FIV, Visna and CAEV, which cause diseases in monkeys, cats, sheep and goats. Almost all organisms, including most viruses, store their genetic material on long strands of DNA. Retroviruses are the exception because their genes are composed of RNA (Ribonucleic Acid). RNA has a very similar structure to DNA. However, small differences between the two molecules mean that HIV's replication process is a bit more complicated than that of most other viruses.

How many genes does HIV have?

HIV has just nine genes (compared to more than 500 genes in a bacterium, and around 20,000-25,000 in a human). Three of the HIV genes, called gag, pol and env, contain information needed to make structural proteins for new virus particles. The other six genes, known as tat, rev, nef, vif, vpr and vpu, code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease. At either end of each strand of RNA is a sequence called the long terminal repeat, which helps to control HIV replication.

HIV LIFE CYCLE:ENTRY:-

HIV can only replicate (make new copies of itself) inside human cells. The process typically begins when a virus particle bumps into a cell that carries on its surface a special protein called CD4. The spikes on the surface of the virus particle stick to the CD4 and allow the viral envelope to fuse with the cell membrane. The contents of the HIV particle are then released into the cell, leaving the envelope behind.

Reverse Transcription and Integration:Once inside the cell, the HIV enzyme reverse transcriptase converts the viral RNA into DNA, which is compatible with human genetic material. This DNA is transported to the cell's nucleus, where it is spliced into the human DNA by the HIV enzyme integrase. Once integrated, the HIV DNA is known as provirus.

Transcription and Translation:HIV provirus may lie dormant within a cell for a long time. But when the cell becomes activated, it treats HIV genes in much the same way as human genes. First it converts them into messenger RNA (using human enzymes). Then the messenger RNA is transported outside the nucleus, and is used as a blueprint for producing new HIV proteins and enzymes.

Assembly, Budding and Maturation

This electron microscope photo shows newly formed HIV particles budding from a human cell.

Among the strands of messenger RNA produced by the cell are complete copies of HIV genetic material. These gather together with newly made HIV proteins and enzymes to form new viral particles, which are then released from the cell. The enzyme protease plays a vital role at this stage of the HIV life cycle by chopping up long strands of protein into smaller pieces, which are used to construct mature viral cores. The newly matured HIV particles are ready to infect another cell and begin the replication process all over again. In this way the virus quickly spreads through the human body. And once a person is infected, they can pass HIV on to others in their bodily fluids.

Types of HIV/AIDS:

Pneumocystitis carinii pneumonia related HIV Tuberculosis related HIV Toxoplasmosis related HIV Kaposi sarcoma related HIV Cryptosporidiosis related HIV Herpes zoster related HIV Hemophiliacs related HIV HIV-1 HIV-2

CAUSES OF HUMAN IMMUNODEFEFECIENCY VIRUS INFECTION:

The virus has two major strains: HIV-1, which is closely related to the primate retrovirus called simian immunodeficiency virus, and HIV-2, which is associated with immunodeficiency but less pathogenic that HIV-1, results from infection with HIV, which strikes cells bearing the CD4+ antigen; the latter (normally a receptor for major histocompatibility complex molecules) serves as a receptor for the retrovirus and lets it enter the cell. HIV prefers to infect the CD4+ lymphocyte or macrophage but may also infect other CD4+ antigenbearing cells of the GI tract, uterine cervical cells, and neuroglial cells. The virus gains access by binding to the CD4+ molecule on the cell surface along with a co-receptor (thought to be the receptor

CCR5). After invading a cell, HIV either replicates, which leads to cell death, or becomes latent. HIV infection leads to profound pathology, either directly, through destruction of CD4+ T cells, other immune cells, and neuroglial cells, or indirectly, through the secondary effects of CD4+ T-cell dysfunction and resultant immunosuppression. The infection process takes three forms: immunodeficiency (opportunistic infections and unusual cancers) autoimmunity (lymphoid interstitial pneumonia, arthritis, hypergammaglobulinemia, and production of autoimmune antibodies) neurologic dysfunction (AIDS dementia complex, HIV encephalopathy, and peripheral neuropathies).

TRANSMISSION:HIV is transmitted by direct inoculation during intimate sexual contact, especially associated with the mucosal trauma of receptive rectal intercourse; transfusion of contaminated blood or blood products (a risk diminished by routine testing of all blood products); sharing of contaminated needles; or transplacental or postpartum transmission from an infected mother to the fetus (by cervical or blood contact at delivery and in breast milk). HIV isnt transmitted by casual household or social contact. The average time between exposure to the virus and diagnosis is 8 to 10 years, but shorter and longer incubation times have also been recorded. Most people develop antibodies within 6 to 8 weeks of contracting the virus.

SYMPTOMS:The symptoms of HIV infection are the result of HIV attacking the cells of the body's immune system. Early in the disease, many people with HIV infection have no symptoms. Some people may experience flu-like symptoms that occur about four to eight weeks after infection. Symptoms may include swollen glands, fever, headache and fatigue.

Later AIDS symptoms - The progression of HIV to full AIDS causes many symptoms:

Opportunistic infections Coughing Shortness of breath Seizures Lack of coordination Difficult swallowing Painful swallowing Mental symptoms Confusion Forgetfulness Severe and persistent diarrhea Fever Night sweats Vision loss Nausea Abdominal cramps Vomiting Decreased appetite Mouth white spots Unusual mouth blemishes Skin lesions Weight loss Extreme fatigue Severe headaches Coma Kaposi's sarcoma Cervical cancer Lymphoma

Infant and childhood HIV symptoms - HIV symptoms in infants and young children
No early symptoms - There are often no early signs of HIV in infants. Failure to thrive Slow weight gain Sickly child Delayed development Delayed crawling Delayed walking Delayed speaking Neurologic problems Difficulty walking Poor school performance Seizures Symptoms of HIV encephalopathy

Opportunistic infections Conjunctivitis (pink eye) Ear infections Tonsillitis

ACQUIRED IMMUNODEFECIENCY SYNDROM: Causes and incidence:AIDS results from infection with HIV, which has two forms: HIV-1 and HIV-2. Both forms of HIV have the same modes of transmission and similar opportunistic infections associated with AIDS, but studies indicate that HIV-2 develops more slowly and presents with milder symptoms than HIV-1.

THE ORIGIN OF AIDS:

At this time, most evidence suggest that AIDS has it roots in Africa. This is believed because certain Simian Immunodeficiency Viruses (SIVs) are closely related to HIV and HIV-2, for instance, has an almost exact counterpart in a virus of the sooty-mangabey, a type of African monkey. The HIV-2's connection to the sooty mangabey is probably the most compelling evidence for animal to man transfer of HIV. A likely source of HIV-1 has been more difficult to pin down. The closest simian virus to HIV-1 discovered to date exists in certain chimpanzees. Scientists have long recognized the ability of certain viruses and other diseases to pass from animals to humans. This process is referred to as zoonosis. Once an animal disease has infected people, it may then be passed from human to human. Although it has not been proven that HIV came from primates, an SIV has been known to infect humans. The earliest and most compelling evidence of HIV infection is that of an adult male who lived in what is now the Democratic Republic of Congo. Scientists recently succeeded in isolating the virus from a plasma sample taken from the man in 1959. Researchers believe that the ancestor of this strain may date to the 1940s or 50s and was introduced into humans a decade or more earlier. In June and July of 1981, cases of an extremely uncommon opportunistic infection, Pneumocystis carinii pneumonia, and a very rare skin tumor of endothelial cell origin, Kaposi's sarcoma, were first reported in New York and California in epidemic proportions among previously healthy young homosexual and bisexual men who were not previously known to be predisposed to these diseases.With the rapidly increasing

number of cases, it was soon recognized that other life threatening infections and neoplastic diseases were also observed and found to be associated with an unexplained defect in cell mediated immunity, common to each of these patients. By early 1982 the group of disease entities was named the acquired immune deficiency syndrome (AIDS) by the Center for Disease Control (CDC). The term "syndrome" has been used because AIDS does not constitute a single illness, but rather encompasses a wide range of clinical diseases including specific life threatening infections and neoplasm's associated with a profound and irreversible unexplained acquired disorder of cell mediated immunity. Since the appearance of the original definition in September of 1982, the CDC has subsequently revised this definition to accommodate additional syndromes recognized as manifestations of advanced HIV disease. When the first cases of AIDS were reported, many hypotheses were proposed to explain the possible causes of the newly recognized syndrome, but it is now widely accepted that AIDS is caused by a previously unknown human retrovirus, which was initially discovered and isolated in 1983 from patients with persistent generalized lymphadenopathy at the "Institut Pasteur" in Paris. All the related viruses which were discovered were named the human immunodeficiency virus (HIV) by the International Committee on the Taxonomy of Viruses in 1986.

TERMINOLOGY:AIDS: The syndrome called AIDS (Acquired Immuno Deficiency Syndrome) is the late stage of HIV disease. ARC: The term AIDS Related Complex has been abandoned, because the signs labeled with this term are manifestations of the middle stage of HIV disease.

The list of risk factors mentioned for HIV/AIDS in various sources includes:
Injection drug use Homosexual behavior Needle-stick injury - rare transmission STDs - having other STDs makes catching HIV more likely during sex.

Syphilis Genital herpes Chlamydial infection Gonorrhea Bacterial vaginosis Blood exposure Injection drug use Needlestick injury Mother-infant transmission Breastfeeding transmission Mother-to-fetus transmission

Effects of HIV on nutrition Body changes:A man suffering wasting related to HIV and TB infection

AIDS is well known for causing severe weight loss known as wasting. In Africa, the illness was at first called slim because sufferers became like skeletons. Yet body changes are not only seen during AIDS; less dramatic changes often occur in earlier stages of HIV infection. Whereas starving people tend to lose fat first, the weight lost during HIV infection tends to be in the form of lean tissue, such as muscle. This means there may be changes in the makeup of the body even if the overall weight stays the same. In children, HIV is frequently linked to growth failure. One large European study found that children with HIV were on

average around 7 kg (15 lbs) lighter and 7.5 cm (3 inches) shorter than uninfected children at ten years old. What causes these changes? One factor behind HIV-related weight loss is increased energy expenditure. Though no one knows quite why, many studies have found that people with HIV tend to burn around 10% more calories while resting, compared to those who are uninfected. People with advanced infection or AIDS (particularly children) may expend far more energy. But faster metabolism is not the only problem. In normal circumstances, a small rise in energy expenditure may be offset by eating slightly more food4 or taking less exercise.5 There are two other important reasons why people with HIV may lose weight or suffer childhood growth failure.6 The first factor is decreased energy intake or, to put it simply, eating less food. Once HIV has weakened the immune system, various infections can take hold, some of which can affect appetite and ability to eat. For example, sores in the mouth or throat may cause pain when swallowing, while diarrhoea or nausea may disturb normal eating patterns. Someone who is ill may be less able to earn money, shop for food or prepare meals. Stress and psychological issues may also contribute. Secondly, weight loss or growth failure can occur when the body is less able to absorb nutrients particularly fat from food, because HIV or another infection (such as cryptosporidium) has damaged the lining of the gut. Diarrhoea is a common symptom of such malabsorption. Antiretroviral treatment:Taking antiretroviral drugs on an empty stomach is like digesting razor blades. PILLS AND TREATMENT:There is no cure for AIDS. However, treatment with antiretroviral drugs can delay the onset of AIDS and allow someone to live with

HIV for many years without becoming ill. This usually means taking a combination of three or more drugs at least once a day.

What is HIV antiretroviral drug treatment?

This is the main type of treatment for HIV or AIDS. It is not a cure, but it can stop people from becoming ill for many years. The treatment consists of drugs that have to be taken every day for the rest of a persons life. The aim of antiretroviral treatment is to keep the amount of HIV in the body at a low level. This stops any weakening of the immune system and allows it to recover from any damage that HIV might have caused already. The drugs are often referred to as: antiretrovirals ARV anti-HIV or anti-AIDS drugs

First and second line therapy:At the beginning of treatment, the combination of drugs that a person is given is called first line therapy. If after a while HIV becomes resistant to this combination, or if side effects are particularly bad, then a change to second line therapy is usually recommended. Second line therapy will ideally include a minimum of three new drugs, with at least one from a new class, in order to increase the likelihood of treatment success.