An Answer Appears

This is the fourth post in The Scope blog series “HIV: A Scientific Discovery,” a collection of pieces that explore the major scientific milestones in the discovery of the HIV virus. 

The verdict was out: a virus was behind the AIDS outbreak. But which virus? Was it a new powerful strain of a well-known virus? Or was it something entirely new? Amidst the AIDS panic, scientists turned to the only thing they had: hints from history and previous research. Could their knowledge of previously characterized viruses provide any clues? Luckily, the answer was yes.

Most viruses are simply strings of DNA floating in a specialized bubble of membrane material. They inject their DNA into other cells, which unknowingly transcribe the DNA into an intermediate genetic molecule called RNA before translating these RNA viral “messages” into viral proteins. These proteins assemble into new viral bubbles that bore their way out of the cell, spread to other cells, and continue their parents’ conquest.

However, some viruses don’t contain DNA but instead carry genetic information in the form that is traditionally intermediate, RNA. These viruses convert their RNA into DNA using reverse transcriptase, a special enzyme absent from host cells, earning them the name “retroviruses.” The viral DNA intermediate is then physically pasted into the host’s genome, existing no longer as a foreign object inside a cell but instead as an actual part of the cell. Thus, unlike regular viruses, retroviruses don’t just hijack a cell’s machinery; they hijack its identity.

By disrupting cells’ genetic information, retroviruses essentially cause mutations that can launch cells down a path of rapid growth and division, a condition commonly known as cancer. For decades, retroviruses had been known to cause leukemia, a cancer of rapidly growing white blood cells, yet retroviruses had never before been associated with any kind of depletion in cells – at least not in humans.

In the mid to late 1900s, domestic cats were often plagued with infections by Feline Leukemia Virus (FeLV), a retrovirus that not only caused leukemia but also effected immune disorders that were characterized by a depletion and dysregulation of the immune system’s T cells. Infected cats often fell victim to opportunistic infections similar to the Pneumocystis carinii Pneumonia that preyed on many AIDS patients. Though FeLV was clearly not the virus responsible for AIDS, scientists found the symptoms eerily suspicious.

At the time, the only retrovirus family identified in humans was the Human T-lymphotropic Virus (HTLV), a virus known to cause leukemia in humans but not yet found to be associated with any degree of immune deficiency. The virus’ selective preference for attacking T cells offered a convincing explanation for the near-lack of T cells in AIDS patients. How the virus did this exactly would not be known for several more years, but slight speculation immediately revealed a potential mechanism for how a virus that usually caused cancer could suddenly spark an outbreak of immune deficiency.

As was mentioned in “A Crossing of Maladies” two posts ago, the immune deficiency seen in AIDS was not simply a matter of fewer T cells; the T cells themselves were abnormal and somehow unable to respond to their environment. Retroviruses offered the perfect explanation. If they could cause cancerous mutations in white blood cells, the viruses could technically cause any types of mutations in any other types of cells. In the case of AIDS, HTLV would have simply inserted its own DNA sequence into a part of the cell’s genome that was crucial for immune function instead of one involved in cellular division.

Another clue came once again from epidemiology. HTLV infections, while not widespread in the US, were quite commonplace in Haiti. Coincidentally, behind homosexuals and intravenous drug users, Haitian immigrants were the largest group of AIDS patients in the US. Had a new strain of HTLV capable of causing immune deficiency arisen in Haiti and migrated to the US within their immigrating hosts?

By the start of 1983, less than 2 years after the first case of AIDS was diagnosed, scientists had already arrived at a highly convincing candidate for “the AIDS agent:” HTLV. This realization was a triumphant testament to the power of steady progress in basic scientific research. Nearly a decade earlier, Dr. Robert Gallo, researcher at the National Cancer Institute, had painstakingly isolated and developed ways to grow the HTLV virus, a virus that only now proved to be a major health concern in the US. For decades, veterinary scientists had treated a viral infection found exclusively in cats only to find later on that the accumulated knowledge concerning the FeLV virus was pivotal in revealing the cause behind one of the biggest outbreaks of disease in human history.

Basic scientific research had poised the scientific community to reach an answer to the AIDS outbreak at record pace. All that was left to do was to find the new strain of HTLV, for whose identification lab tests had already been developed thanks to the previous work of Robert Gallo. After the new strain was identified, it would be only a few years until treatments and vaccines became available. As incredible as it seemed, the end was already near when the story had barely begun.

Coming up next week: Scientists begin attempts to isolate the newly suspected HTLV strain from AIDS patients, a task that proves to be more challenging than they expected…

Kevin Wang is a junior in Ezra Stiles College. Contact him at kevin.wang@yale.edu.

(Featured Image courtesy of Wikimedia Commons)