07 April 2012

HIV: Scourge of Humanity

This essay was a term paper for Immunology and Serology class in the fall semester of 2008.

In the summer of 1981, I had just graduated from high school and was travelling to Costa Rica for three weeks then around the entire state of Tennessee for the rest of the summer, keeping up with news in a few areas I was interested in as a future political science student at the University of Tennessee at Chattanooga, such as the conflicts in Central America (El Salvador, Guatemala, Nicaragua) and the early days of the Ronald Reagan administration, along with the ongoing hunger strike in the H-Blocks at Long Kesh in Northeast Ulster (Northern Ireland).

As a consequence of reading numerous news magazines, such as Newsweek, to keep up with those events, I came across an article about a report released by the Centers for Disease Control and Prevention (CDC) about a cluster of five gay men in Los Angeles, California, who had an uncommon pulmonary disease called Pneumocytstis carinii pneumonia (PCP), something usually only seen in persons with severely compromised immune systems such as chemotherapy patients, transplant recipients, or those with Severely Combined Immune Deficiency Syndrome (SCIDS).

A little later, physicians in New York City (primarily) noted a number f cases of young gay men afflicted with Kaposi’s sarcoma, a skin cancer caused by HHV-8 (human herpes virus-8), usually only seen in elderly men.  Almost simultaneously physicians in California noted ten more cases of PCP in young gay men.  The rise of new cases snowballed.

The date of the afore-mentioned CDC report was 5 June 1981, a date which marks not only the agreed-on start-date of the AIDS (Acquired Immune Deficiency Syndrome) pandemic, but also the reincarnation of the field of immunology into how we now know it as well as the birth of such now-commonplace healthcare procedures and the Universal Precautions.

The five cases mentioned in the report were the first cluster of cases in a series of isolated incidences of patients with seemingly good health succumbing to infections and diseases that were easily dispatched by the immune systems of most people the previous decade.  But as the first identified cluster of cases, it was the first signal that the world health community, at least in the developed world, had a major crisis on its hands.

In truth, African nations, especially those of the sub-Saharan region, had been suffering from AIDS for what we now know was nearly a century by then; levels of infection reached epidemic proportions in the Belgian Congo around the year 1960.  Two of the most “ancient” samples of Human Immunodeficiency Virus (HIV), the virus which eventually leads to AIDS, from deceased persons (1959 and 1960 respectively) in Kinshasa, Democratic Republic of Congo (DRC) were studied, dissected, and compared for genetic deviation.

It was determined by the degree of deviation between the two samples that they had evolved from a common ancestor dating back to the 1880’s, when the DRC had been a colony of the Belgian crown and the city of Leopoldville was built.  The conditions resulting from this concentration of humans in that area provided fertile ground in which the pathogenicity of a then-relatively benign (or at least much less virulent) virus mushroomed exponentially. 

Still, the disease remained relatively isolated and a largely local problem easily ignored by the rest of the world until the building of the Kinshasa Highway between the Congolese city and Mobutu, Kenya.  This coincided with the Ground Zero event of the American Bicentennial celebration in New York City, a gathering of four friends, all gay men, one of whom was later determined to be “Patient Zero”.  Gayton was a French-Canadian flight attendant who had worked several flights to Africa landing in Kinshasa and Mobutu and was directly connected to over four hundred of the first American victims of AIDS.

Virologists have demonstrated that HIV evolved out of a similar virus among other primates which was relatively benign (at least in comparison to what HIV does to nearly all humans it infects) called Simian Immunodeficiency Virus (SIV), and was transmitted corss-species through zoonosis.  It has also been determined that the ultimate ancestor of today’s SIV was a fragment of DNA of the lemur on Madagascar broken off 1.8 million years ago.

Two major strains of HIV exist, one of which is less immunogenic and less pathogenic though still deadly (HIV-2), and the other the major cause of AIDS world-wide (HIV-1).  In addition to SIV and the two strains of HIV, another virus with aspects of both SIV and HIV termed Simian-Human Immunodeficiency Virus (SHIV) has been discovered among monkeys in West Africa. 

The strain found in North America is almost always HIV-1, of which there are three groups (M, N, and O), the first of which, Group M, has eleven subtypes, with Subtype B being the overwhelmingly dominant subtype.  HIV-2 is usually found only in West Africa, and if seen in the USA the patient is likely either from West Africa or has had sexual or similar close contact with someone from there.

Incidentally, not one single human in history have ever been infected by a virus; a virion does not become a virus until after infecting the host. 

The HIV virion is composed of a lipid membrane which is studded with docking glycoproteins (gp) called gp120 that are attached to the cell membrane with transmembrane gp’s named gp41 and which contain a nucleus surrounded by a protein-24 (p24) capsid surrounding not DNA but RNA and an ezyme called reverse transcriptase, making it a retrovirus, so-called because its replication process is RNA-to-DNA rather than DNA-to-RNA.

After the reverse transcriptase replicating its own DNA before replicating itself and integrating into the DNA of the host cell, whereupon it replicates the viral RNA to assemble into more virions using material taken from the host cell, which is eventually depleted to the point of necrosis, and eventually leave the host cell to infect other cells.

HIV primarily attacks the CD+ T-lymphocyte, using the CD4 receptor to gain entrance into th interior of the target T-cell via interaction of its gp120 with the CD4 molecule and either the chemokine co-receptor CCR5 or the CXCR4.  HIV invades other cells such as macrophages, microglial cells, peripheral blood monocytes, and the various other cells of the reticulo-endothelial system which have these receptors, but T-helper cells are its favorite meal. 

M-tropic (aka R5) strains of HIV-1 use CCR5 as a co-receptor while T-tropic (aka X4) strains CXCR4.  This is important because a large number of person of Northern and Western European descent lack the gene which produces CCR5 and are thus virtually immune from the R5 strains.

The CD4 receptor is the particular target of HIV because of its affinity for HIV’s gp120 surface molecules.  The CD+ T-cells are, of course, rapidly destroyed by this process, with other cells of the immune system (such as CD8+ T-cells) also being affected.

When the CD4+ T-cell count falls below 200/mcL (a condition called lymphocytopenia), that is the point at which an infection by HIV officially become AIDS.  However, just as no one has ever been infected by a virus (rather by virions), AIDS has yet to kill any human.  It is instead the opportunistic infections which the destruction of the immune system caused by the HIV allows to enter the body which lead to the death of the human host.  These infections are called opportunistic because they are helpless against the defense of a stable immune system and can only infect the host because of a lower threshold of his or her compromised immune system.

Some of these opportunistic infections include Pneumocystis pneumonia (previously thought to be caused by the P. carinii parasite but now known to be caused by P. jirovecii, a yeast-like fungus, but still called PCP), various kinds of candidiasis (infection by a fungus from the genus Candida), extrapulmonary cryptococcosis (infection by a fungus from the genus Cryptococcus), disseminated coccidiodomycosis (infection by a fungus from the genus Coccidiodes),  toxoplasmosis (infection by the protozoa Toxoplasma gondii), Kaposi’s sarcoma, cytomegalovirus (CMV, aka Human Herpes Virus-5, or HHV-5) and other herpes viruses, HIV encephalopathy, histoplasmosis (infection by the fungus Histoplasma capsulatum), aspergillosis (infection by fungus of the genus Aspergillus), and countless others.

A serious and growing danger that is rapidly becoming the single-most dangerous and widespread opportunistic infection attacking AIDS victims is pulmonary tuberculosis caused by Mycobacterium tuberculosis, producing new strains of that disease once thought to be under control which are completely resistant to usual treatment as well as more virulent.

Seroconversion, the point at which antibodies normally become present in sufficient quantity to detect, usually occurs three to twelve weeks after infection, but this can be delayed for up to six months.  The initial test for HIV antibodies is the enzyme-linked immunosorbent assay (ELISA), as has been the case since the early 1980’s, though a recently FDA-approved test called the Ora Quick Rapid HIV-1 antibody test can also be used. 

Since false-positive as well as false-negative results can occur for a variety of reasons, positive results should be confirmed by at least one other test, preferably a Western blot test in which HIV-1 viral antigens are electrophoresed on SDS gel then incubated.  Positive result for gp41 (from the HIV membrane) and/or p24 (from the capsid of its nucleus) are considered valid confirmation or the positive ELISA result.  Tests for the HIV antigen include the EIA test for the p24 antigen, DNA amplification by PCR (polymerase chain reaction, useful for quantifying the amount of HIV RNA in the patient’s plasma, assessing viral therapy, and predicting progression of the disease), and immunoflourescent assay (IFA) using p17 or p24 antibody to treat infected cells.

As for transmission of the disease, sexual transmission is overwhelmingly the main means of transmission, followed by mother-to-fetus and mother-to-infant transmission, blood transfusion, organ transplant, and occupational exposure.  However, according to the CDC, due to the fact that blood supplies in lesser-developed countries were not (and in some countries still are not) routinely tested, nine out of ten HIV-infected persons world-wide got their infection from a transfusion.

Currently, there is no vaccine against HIV and much more controversy about ongoing tests to date.  However, scientists representing different institutions around the country have recently discovered that the Apobec3 family of proteins encodes for Rfv3, a  gene which neutralizes the function of retroviruses, the gene present in the 2% of the HIV-infected population which never displays any sign of the disease.


Avasthi, Amitabh.  “HIV/AIDS Emerged as Early as 1880’s”.  National Geographic News, 1 October 2008. http://news.nationalgeographic.com/news/2008/10/081001-hiv-aids-africa.html .

Koehler, Amanda.  “The Quest for an AIDS Vaccine: the Controversy Continues”.  Advance for Medical Laboratory Professionals, Vol. 20, No. 17, pp. 20-23.  (King of Prussia: Merion Publications, Inc., 2008).

Pratt, Robert J.  HIV and AIDS: A foundation for nursing and healthcare practice, Fifth Edition.  (London: Arnold, 2003).

Santiago, Mario L., et al.  “Apobec3 encodes Rfv3, a Gene Influencing Neutralizing Antibody Control of Retrovirus Infection”.  Science Magazine, Vol. 321, 5 September 2008, pp. 1343-1346.  (Washington: American Association for the Advancement of Science, 2008).

Shilts, Randy.  And the Band Played On: Politics, People, and the AIDS Epidemic.  (New York: St. Matin’s Press, 1987).

Turgeon, Mary Louise.  Immunology and Serology in Laboratory Medicine, Third Edition.  (St. Louis: Mosby, Inc., 2003).

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