In some way or another, most people are familiar with, or have at least heard of, the Human Immunodeficiency Virus (HIV) that gives rise to Acquired Immunodeficiency Virus (AIDS). This is no surprise because since the start of the epidemic, more than 35 million people have died from AIDS-related illness. Although we have yet to develop a vaccine or therapy that completely prevents infection or eradicates the virus, current treatment for HIV infection is extremely effective in suppressing viral replication and allows infected individuals to live relatively normal lives (take Magic Johnson, for example).
That said, not many people are familiar with the basics of HIV. How does the virus work? What types of cells does it infect? Is anyone immune to infection? How is the virus transmitted? How’s at the highest risk? This article will serve as the first in a mini-series titled “The Basics of HIV” where I’ll discuss the biological properties of the virus, but also the highly complex social aspect of this sexually transmitted disease. The field of HIV/AIDS is huge. I’m still learning new things about this disease every day, so I hope you’ll join me in this mini-series to flesh out the “need to knows” about arguably the most impactful epidemic of the 21st century.
Before getting into HIV specifically, let’s start with re-introducing a basic concept about viruses. Remember back to 7th grade biology when you debated about whether or not a virus was a “living creature.” What was the ideology behind that argument? Well, it’s pretty simple. Viruses cannot replicate separate of a host. All viruses carry some form of a genome (the type of genome can vary between types of viruses), but they cannot replicate their genetic code without the help of host DNA replication machinery. This means when HIV infects humans, it uses are DNA replication machinery to replicate its genome and make more of itself…that cheeky bastard.
Now that we understand this basic concept, the genetic code and various proteins that comprise an individual HIV virion will make much more sense. So, let’s quickly list out the important ones and explore their importance to infection. To make it easier to follow along, I’ve labeled the various parts of an HIV virion with letters corresponding to their description in this text. A) The envelope protein, or sometimes referred to as “Env”, is absolutely essential for viral infection. The envelope protein binds to the primary receptor CD4 and one of two secondary receptors CCR5 or CXCR4 to facilitate viral fusion to the host cell membrane. Only upon fusion of the viral membrane to the host membrane can the virus release its contents into the host cell to eventually make more virus. Without fusion, HIV infection cannot occur (a cool Pixar-inspired animation of this process can be watched here). This means that only cell types that have the CD4 and CCR5/CXCR4 surface receptors can be infected by HIV-1. The cells that express these cells most often are immune cells called T-cells, which explains why the immune system becomes compromised during infection, but other cells such as macrophages, microglia, and monocytes can become infected as well.
When the virus fuses, it releases its pre-packaged contents into the cell and gets to work. First, the B) RNA genome is reverse transcribed into viral DNA using a viral enzyme called C) Reverse transcriptase. This process is referred to a reverse transcription because usually DNA is transcribed into RNA which is then translated into proteins. In this case, the virion contains the HIV genome in the form of RNA, so it much be converted back into DNA before it can be integrated into the human genome, which is also made of DNA. This brings us to our next essential viral enzyme, D) Integrase. Once the viral genome has been in turned into DNA, integrase makes cuts in the human DNA genome and inserts the viral genome. After this happens, whenever human DNA is replicated so is the HIV genome, and this is the HIV makes new virus. The last essential viral protein E) Protease. After the HIV proteins have been made using host machinery, the HIV protease cleaves the proteins into their functional forms. Altogether, these proteins then traffic to the membrane of the infected cell and begin to assemble and new virion that will eventually bud off and go on to infect new cells.
These are the biological basics of HIV infection: entry, reverse transcription, integration, protein processing, viral assembly, then budding. Now that we’ve established a strong foundation for how HIV works, we can use this understand to dive deeper into this complex disease. Stay tuned for the next article in the Basics of HIV mini-series where I’ll discuss the systemic results of acute and chronic HIV infection and infection is managed in the clinic.