Clearly, HIV/AIDS has had a significant impact on human history in the last three decades. But what do we know about the culprit, the virus itself? How does it kill? How is transmitted? What can we do to stop it? In the following sections, we introduce the biology of the virus responsible for AIDS, which will provide a basis for our discussions of viral replication in later units.

What is HIV? What is AIDS?

As in the case of pathogens discussed in later units, HIV/AIDS terminology is often confused in everyday conversation. HIV and AIDS have become almost synonymous, even though from a biological perspective, they are far from the same. Human Immunodeficiency Virus (HIV) is the infectious agent responsible for Acquired Immune Deficiency Syndrome (AIDS). “HIV positive” does not necessarily mean that someone also has AIDS- just that s/he will potentially develop the illness.

Incidentally, the term “syndrome” is actually outdated. Typically, a “syndrome” is a set of clinical symptoms for which the cause is unknown. In the early 1980s, when scientists hadn’t yet identified HIV as the cause of AIDS, physicians could only observe the effects of HIV infection, not the transmission of the virus. As a result, they called it a syndrome, because they didn’t know that all the various infections they observed in AIDS patients were caused by a common virus³⁵. Now that the details of the pathology of the HIV virus are known, AIDS can be labeled as a disease. Indeed, a better name for AIDS might be “HIV Viral Disease.”³⁵

“No One Dies of AIDS”³⁶

This quote, taken from the pages of the New York Times, isn’t just journalistic exaggeration. As will be illustrated below, AIDS doesn’t actually kill its victims, but merely leaves them helpless to ward off other opportunistic infections by organisms that wouldn’t ordinarily cause disease but do so when an individual’s immune system is too weak to fight pathogens³⁷. However, before we launch into further detail, it is useful to keep the following principles in mind.

1. One disease, many treatments: Even though the HIV virus itself cannot be entirely removed from a patient’s body as yet, the prevention of opportunistic infections can greatly extend the lifespan of those afflicted with AIDS. The use of an entire “pathogen arsenal” – antibacterial, antifungal, antiparasitic drugs – may improve a patient’s ability to resist other opportunistic infections, and, as a result, prolong life.
2. AIDS can “interact” with other diseases: This was demonstrated by the concurrence of the AIDS epidemic with the emergence of drug resistant strains of tuberculosis in the early 1990s.³⁸ Strategies to combat AIDS are necessary not just for their own sake, but also because immune-compromised patients may effectively serve as “reservoirs” for other pathogens to propagate.
3. Each AIDS patient may have different symptoms: Related to the point above, each patient, though they are infected with the same virus, may experience different symptoms based on the opportunistic pathogens that colonize their body. Thus, each case is in some sense an individual disease.

Keep these in mind when thinking about the biology of HIV/AIDS, and you should have a better appreciation for how treatment is practiced. First, though, it is necessary to understand the pathogen responsible for this disease: the HIV virus.

A Virus

Viewed under a powerful microscope, a virus doesn’t seem like much: just a tiny shell of protein covering the nucleic acid of its genome. A genome, in turn, is just the entire genetic sequence of an organism encoded in DNA or RNA. The smallest of all pathogens, they are measured in fractions of a micron³⁹. Yet, despite their size, viruses actually constitute the largest biomass on the planet⁴⁰. Additionally appearances can be deceiving since even this minute clump of protein and nucleic acid can ravage the human body, slipping inside cells and replicating at a frightening rate.

The small size and relative simplicity of viruses raises an important question: are they alive? Like higher organisms, viruses have DNA or RNA genomes. In other aspects though, viruses deviate wildly from what is traditionally regarded as “life”⁴¹. They don’t grow. They don’t carry out metabolic activities like glycolysis or respiration. They don’t respond to environmental stimuli. They don’t have limbs or flagella to propel them through their environment. In fact, they are not even composed of cells! Yet, viruses can replicate, doing so by hijacking the molecular machinery of the host cell³⁹. So are they alive? By traditional definitions, no – but these criteria were based on the characteristics of larger organisms. If instead the criteria for life are based on the smallest known life forms (like viruses), then the only real requirement becomes replication, with viruses forming a class of “acellular” organisms.

Viruses are found in many different shapes and sizes. Classes of different viruses can be characterized by identifying factors including their genome type (i.e. single- or double-stranded RNA or DNA), mode of replication, and whether it is typically surrounded by a plasma membrane derived from its host cell. Specifically, the HIV virus possesses a single-stranded RNA genome and replicates through a DNA intermediate through the actions of the enzyme reverse transcriptase. Because of these properties, HIV is also known as a retrovirus. Other classes include viruses with double-stranded DNA genomes (e.g. smallpox and herpes virus) and viruses with single-stranded RNA genomes (Ebola and influenza).

A virus exists in two forms: one, in which a mobile virion (single virus) drifts outside a host cell and the second, in which the virus invades a host cell and replicates⁴². For HIV, this time inside a host cell is further divided into the latent and lytic stages. During the latent stage, the viral genome remains unreplicated inside the host – in the case of HIV, for up to a decade⁴³. While it isn’t replicating, it is invisible to the immune system⁴³. This situation is reversed during the lytic stage when the virus replicates, overwhelming the host cell and causing the cell to burst. This cell lysis releases a surge of virions that can go on to infect other host cells⁴⁴. Together, these phases form a carefully orchestrated set of biochemical events, not unlike a symphony with two movements. At
each stage, HIV acts as a conductor, directing its host cell in the complex task of hiding and then replicating the tiny invader.

Comprehension Questions:
1. What shapes can a virus have?
2. What does it mean to be an obligate intracellular pathogen?
3. What characteristics are used to classify a virus?
4. What are the general characteristics of the “viral life cycle”?