In 1984, the United States announced the discovery of the source behind the Acquired Immunodeficiency Syndrome (AIDS) outbreak that occurred in West Africa throughout the decade. Thanks to the work of Françoise Barré-Sinousssi and Luc Montagnier, an isolated strain of the virus was taken from a deceased patient and later named the Human Immunodeficiency Virus (HIV) (Smith 2003). The National Cancer Institute announced that a vaccine for the virus would be available to the public within two years. A decade later, President Clinton promised an HIV vaccine would be ready within ten years. Thirty-one years have passed from the discovery of HIV and a vaccine is still not available while the worldwide death count of HIV has reached over 35 million. Billions of dollars have been donated to HIV research thanks to high-profile cases like the deaths of celebrities like Freddie Mercury and Liberace (Smith 2003). To understand the difficulty in producing a vaccination to fight HIV, the disease’s background and transmission must be understood. The difficulty for immunology scientists when confronting this virus lies in its common ancestor: Simian Immunodeficiency Virus (SIV).
THE DEVELOPMENT AND HISTORY OF HIV
There are two known strains of HIV: HIV-1 and HIV-2. Though both are very similar they have different origins. HIV-1 is very similar to SIV found in Common Chimpanzees (Pan troglodytes) from West and Equatorial Africa. Evidence suggests HIV-2 originates from Sooty Mangabeys (Cercocebus atys) but is also found in several species of Macaques (Sharp 2001). SIV underwent cross-species transmission likely because of poaching. Illegal hunters will kill African primates and sell the meat at markets labeled as ‘bush meat.’ If the meat is improperly handled or prepared, blood or mucosal secretion can result in the contraction of a foreign disease. Another possible method for how HIV-1 transmitted across species is iatrogenic modes. Journalist Edward Hooper in his book The River proposed HIV originated in apes and became a human virus during Polio vaccine testing in the Congo. The research team used a primate facility for Polio vaccine testing and harvested kidneys for vaccine production. If these primates carried SIV, then one million people in the Congo, Rwanda, and Burundi who were administered the Polio vaccine could have been contaminated along with vaccine production back in the US and elsewhere in the world. The year of HIV-1 transmission is uncertain but believed to have occurred during the 1920s (Sharp 2001). Researchers of the virus continue to question though why if the disease originated in the 1920s did it take over thirty years to become an epidemic. A possible reason is the HIV-1 strain may have been transmitted from a chimpanzee to a human at different times. Before the 1950s, HIV-1 crossed species lines multiple times but the host died before the virus infected another human. In the 1950s, HIV-1 gained momentum in its infectivity because of new population structures in post-WWII Africa and changing medical interventions that provided an opportunity for rapid spread (Sharpe 2001).
HIV-2 is a less common strain as compared to HIV-1 and mostly exists in West Africa. The origin and start date of HIV-2 is not known but the cross-species transmission is believed to have occurred in the Ivory Coast during the 1930s or 1940s. Sample SIV strains taken from Sooty Mangabeys in the area are the most closely-related strains to HIV-2 that have been found (Sharp 2001).
SIV does not affect primates the same as HIV affects humans. Overtime primates have built a tolerance to the virus (Plantier 2009). When compared, SIV affects a low level of Helper T Cells in hosts while HIV affects a high level of Helper T cells in hosts. SIV replication also remains stable in primates taking decades to progress in hosts while HIV replication in humans increases at an exponential rate. Though primates can contract opportunistic diseases after SIV impairs the immune system, the percentage of times is considerably lower than AIDS development in humans (Pandrea 2008).
THE IMMUNOPATHOGENESIS OF HIV
HIV can be transmitted through blood, semen, rectal or vaginal fluids, and breast milk. The main methods of transmission are currently intercourse and shared injection needles commonly associated with drug injection. HIV’s primary impact on the body is the immune system. Commonly when a foreign virus enters the body, the immune system will tag and destroy the microbe through white blood cells like the Helper T lymphocytes. Helper T cells are part of the adaptive immune system. Helper T cells will draw other white blood cells to a virus through chemotaxis (chemical signaling). The chemical released is Cluster Differentiation 4 (CD4) (Smith 2003). The white blood cells will destroy the virus and other infected cells. Helper T Cells will also induce multiplication of white blood cells through chemotaxis. The new white blood cells are antibodies. Antibodies act as markers which can identify the same virus if it enters the body again and are part of the body’s acquired immunity. If the virus is transmitted again, antibodies will tag microbe for destruction.
When HIV enters the body it travels through the circulatory system. The virus then enters Helper T cells through the envelope glycoprotein GP120 which is exposed on the surface of the virus and binds to CD4 (Letvin 2005). By binding to CD4, GP120 changes and binds to receptors on Helper T cell. The exact receptor is not known but evidence suggests either CCR5 or CXCR4 (Pace 2013). The virus releases of fusion peptides into the Helper T cell causing a fusion of the two cell’s membranes. HIV RNA, specifically the sequence known as long terminal repeat (LTR), will replicate itself and release more HIV microbes into the circulatory system which will repeat the process with other Helper T cells (Letvin 2005). The Helper T cell can no longer perform its vital role in the body’s immune response. Without any way of marking foreign viruses or bacteria, other diseases can take advantage of the weakened immune system and are known as opportunistic infections. Carriers with HIV and one or more opportunistic infections have AIDS.
PROGRESS TOWARDS A VACCINE
No vaccine for HIV is available to the general public today. There are methods to fight the spread of HIV in the body but with limited success. Antiretroviral drugs can inhibit HIV microbes in the body. Fusion entry inhibitors are currently the most popular as they prevent HIV from binding to Helper T cells (Song 2013). There are also other antiretroviral drugs though like reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors which prevent the assembly and spread of HIV microbes in the body. These drugs do not remove HIV from the host but inhibit its progress.
The goal for the medical community though is to develop a method to prevent the further spread of HIV on a global scale. The most promising technique is vaccination. One of the world leaders in the race for an HIV vaccine is David Ho. Ho has worked on multiple studies and developments to find promising ways to fight HIV and develop a vaccine. His work has been extremely well-funded as well with large grants from the Gates foundation and support from the Chinese and American governments. Currently Ho is developing a drug called Ibalizumab which acts as an antibody. Ho’s research is centered on the HIV-1 strain because of its prevalence worldwide.