By Christian Agosto-Burgos
The Human immunodeficiency virus (HIV) emerged around 1920 in the Democratic Republic of Congo, probably as the result of human consumption of raw or undercooked chimpanzee’s meat contaminated with the Simian Immunodeficiency Virus (SIV). If untreated, HIV can lead to acquired immunodeficiency syndrome (AIDS). HIV did not become a global issue until 1980 when the AIDS crisis emerged. During 1980, HIV became a rapid epidemic and it is estimated to be the cause of death of 675,000 Americans since the first case of AIDS was reported. It is also estimated that around 1.2 million people in the U.S. are living with HIV.
During the last decade, there has been an immense public debate on whether the cure for HIV exists. Many people believe in a conspiracy theory that states the government and pharmaceutical industry are holding the cure for HIV. But, is there really a cure for HIV? In order to answer this question we need to understand how HIV infects and behaves. HIV gain access into the body through blood, semen or vaginal fluid. As all of the other viruses, HIV cannot replicate on its own, therefore it needs a host to replicate and survive. HIV is a retrovirus which means that it only carries its genetic material in the form of RNA, not DNA and RNA as humans do. HIV mainly infects and destroys human CD4 T cells, but also has the availability to infect other cells. When HIV has gained access to the body, it attaches to CD4 T cells through binding to receptors expressed on the surface of CD4 T cells. This leads to the intake of HIV by CD4 T cells through a process known as endocytosis. HIV then disintegrates its envelope proteins and its genetic material in the form of viral RNA becomes freely accessible and converted into viral DNA. HIV’s viral DNA then travels into the nucleus of CD4 T cells and integrates into the cell DNA. This integration now allows HIV to use the cell machinery to replicate and infect other cells (see image below for more details).
HIV infecting a CD4+ T cell: HIV attaches to the membrane of CD4+ T cells by binding its envelope protein GP120 to the CD4 and CCR5 or CXCR4 receptors expressed in CD4 + T cells. This attachment leads to the intake of HIV by the cell through a process known as endocytosis. Once HIV has gained entry into the cell cytoplasm, it disintegrates its envelope making its viral RNA accessible for reververse transcription. During reverse transcription, HIV’s viral RNA is converted into viral DNA. The viral DNA travels into the cell’s nucleus where it becomes integrated into the cell’s DNA. Now, HIV is part of infected cell genome and can use the cell’s machinery to become transcribed into RNA and translated into protein. Once the proteins of HIV are accessible in the cytoplasm, the virus become assembled and released from the cell which give HIV the capacity to infect other cells throughout the body.
The integration of HIV into the human DNA provides this virus with an enormous advantage. HIV now is part of the DNA of HIV-infected cells which makes its eradication from these cells almost impossible. HIV also has incredible high mutation rates of its envelope proteins, gp120 and gp41, which provides the virus with a remarkable capacity to mock the immune system response and to become an escape master. This high mutation rate does not only allow HIV to escape recognition by immune cells, but it also results in a diminished capacity of the body to neutralize the virus. Taken together, these and others factors explain the complexity of HIV and why there is not a cure for it. However, scientists around the world are not giving up yet. Thanks to their discoveries, HIV infection can be controlled with antiretroviral therapy (ART) which in some individual could lead to an HIV stage known as undetectable which means that the replication of HIV within an individual is so slow that the virus cannot be detected in the blood of the infected person. HIV positive individuals with undetectable HIV viral load will not transmit HIV to others. In summary, the biology underlying HIV is extremely complex which results in the lack of a cure. However, scientists are working on new discoveries everyday to cure, prevent and treat HIV.
Edited by Carolina Herrera and Lane Scher