A Blast from the Past

A hot button microbe right up there with MRSA, I’m sure nearly every one of us is mindful of Human Immunodeficiency Virus or HIV. HIV has found our Achilles Heel, as it targets the very cells we trust to protect us from invading microbes and viruses such as itself. But the ingenious of this virus is beyond even these tactics, as HIV is a retrovirus.

This designation does not simply mean that HIV is keeping it fresh with style from the 70s, but rather that HIV has some sweet dance moves that can turn everything we thought we knew on its head!

Retroviruses fall within the virus family, Retroviridae, and typically have a single strand of RNA as their genetic blueprint. While RNA genes instead of DNA genes might seem strange for cellular life, viruses bend the rules a bit. In other words, it is not rebellious for a virus to chose RNA rather than DNA; in fact, it is quite hip. HIV acts as a typical RNA virus, dormant and zombie-like until it snags its favorite flavor of cell surface protein. And just as soon as HIV finagles its way inside its new host, is when the magic happens. The ace hidden up HIV’s sleeve is an enzyme known as RT or reverse transcriptase. As hinted by its name, this is the enzyme that turns the beat around!

Reverse transcriptase begins by taking the single strand of viral RNA and using it to fashion a new strand of DNA. But hold up: this seemingly innocent process is actually quite the stunt! In biology, DNA is used to make RNA, not the other way around. But since reverse transcriptase doesn’t seem to subscribe to the “save the best for last” mentality, it pulls this showstopper seemingly from nowhere. This opening trick, leaves one strand of RNA and one strand of DNA in a hybrid molecule of sorts. This is definitely something you don’t see every day, but if you blink you might miss it, as reverse transcriptase keeps the show entertaining by making the RNA strand disappear.

But RT is a performer of many talents, so it wraps up with a spectacular finale: crafting a new DNA strand from the lone DNA strand to fashion a double-stranded DNA molecule.

And just like that, the magnificent reverse transcriptase has transformed one measly strand of RNA into two DNA strands. But besides the wow-factor, why would HIV want this spectacle? I mean, RNA viruses can replicate themselves perfectly adeptly without reverse transcriptase. The secret that answers this inquiry is that this double-stranded DNA molecule is a clandestine operative that sneaks into a host chromosome and implants itself. Reminiscent of a “prophage,” this viral spy is known as a “provirus” and lays low until it is activated. The provirus unwinds itself and proceeds with copying itself and building new virus particles as any other RNA virus.

This show is full of awe-inspiring surprises, but also chock full of implications. For one, antivirals are few and far between, as when viruses replicate, they use enzymes and machinery from a host cell, and we do not want to inhibit something that might hurt our own cells. But reverse transcriptase is specific to retroviruses such as HIV. This means that even though RT is HIV’s secret agent, it is also its Achilles Heel. AZT is a potent inhibitor of HIV replication as it is able to grab onto and block its reverse transcriptase.

Either way, reverse transcriptase and retroviruses are super fascinating!