Human Immunodeficiency Virus

This time I wanted to share about a general discussion of a very common sexually transmitted disease AIDS.

Human Immunodeficiency Virus

  Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.

HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk.

When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released.

The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell’s membrane. The gag gene directs formation of the proteins of the matrix p17, the “core” capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11.

In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.

Acquired Immunodeficiency Syndrome (AIDS)

When the CD4 lymphocyte count drops below 200/microliter, then the stage of clinical AIDS has been reached. This is the point at which the characteristic opportunistic infections and neoplasms of AIDS appear. The organ involvement of infections with AIDS represents the typical appearance of opportunistic infections in the immunocompromised host–that of an overwhelming infection–that makes treatment more difficult. The strategies employed in AIDS patients to meet this challenge consist of (1) preserving immune function as long as possible with antiretroviral therapies, (2) using prophylactic pharmacologic therapies to prevent infections (such as Pneumocystis carinii pneumonia), and (3) diagnosing and treating acute infections as soon as possible.

Pneumocystis carinii

Pneumocystis carinii is the most frequent opportunistic infection seen with AIDS. It produces a pulmonary infection, called Pneumocystis carinii pneumonia (PCP), but rarely disseminates outside of lung. The most common clinical findings in patients with PCP are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P carinii stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.

Cytomegalovirus

Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm

Mycobacteria

Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.

Fungal Infections

There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung.

Infections with the pathogenic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.

Toxoplasmosis

Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS. The lesions are usually multiple and have the appearance of abscesses. Less commonly, T gondii infection is disseminated to other organs.

Herpes simplex

Herpes simplex virus infection with AIDS is most likely to involve the gastrointestinal tract, mainly the esophagus and the perianal region. Herpes zoster infection of the skin can also occur prior to the onset of clinical AIDS. Herpes infections are rarely life-threatening

Gastrointestinal Protozoal Infections

Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Diagnosis can be made by examination of stool specimens and/or intestinal biopsy.

Malignant Neoplasms

Kaposi’s sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS.

Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.

Miscellaneous

Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.

I tried to write in a very simple way, so that everyone can understand about this disease, but if anyone has any question, feel free to ask me anytime..

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8 Comments

  1. Khushi

    Thank you for this very useful post.

  2. Anonymous

    This is very useful. I did not know all these details – all I knew was it was the transmission mode and that it cant be cured yet. Can you explain how anyone can suspect they have AIDS?

  3. Sarmila

    lot of common symptoms like vomitting , nausea, itching, dizziness , fever , above all an uneasiness in the whole body like body ache, if somone is married feeling like not doing sex and lot of stuff,,
    so we suggest if anyone thinks that he or she may get this disease gofor a regular blood check.. any more qs let me know, i will try to help u out.

  4. Sarmila

    enlarged lymph nodes like in neck, glands is also a major symptom,, diarrehea can occur if anyone is suspected to..

  5. sarmila.basu

    you are welcome..

  6. Yasmin Talgeri

    A very informative post. What are the latest treatment options for HIV+ patients ? We are hearing so much about stem cell research these days…do you think its a good option for the patients?

  7. sarmila.basu

    that strategy is not a cure, may be more effective than antiviral treatments and many have the potential to immunize people against the virus

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