The Human Immunodeficiency Virus (HIV) is a retrovirus, meaning it carries its genetic information as RNA and must convert it into DNA to replicate. This conversion and the subsequent hijacking of the host cell machinery depend entirely on the physical architecture of the virus particle. The unique shape and arrangement of the viral components enable the virus to attach to, enter, and successfully take over the body’s immune cells. Understanding the physical form of the HIV virion is key to developing effective countermeasures.
The Architecture of the HIV Virion
The mature HIV particle, or virion, is roughly spherical, measuring about 120 nanometers in diameter. Its outermost layer is a lipid membrane acquired from the host cell when the virus buds off. This viral envelope is studded with specialized protein complexes that serve as the virus’s primary tools for infection.
These complexes appear as small spikes, each a trimer composed of two types of glycoproteins: gp120 and gp41. The gp120 subunit is the outer surface protein, forming the cap, while gp41 is the transmembrane protein anchoring the complex into the envelope. Beneath the lipid bilayer is a layer of viral protein called the matrix, which maintains the virion’s structural integrity.
The most distinctive internal feature is the conical capsid, a cone-shaped inner shell made of thousands of copies of the capsid protein (p24). The conical capsid acts as a protective container, shielding the viral genetic material and key enzymes from the host cell’s cytoplasm until the correct moment.
Structural Components Critical for Cellular Entry
The process of infection begins with a highly specific interaction between the viral spike proteins and the target cell, typically a CD4+ T-cell. The external gp120 protein binds to the CD4 receptor on the immune cell surface, which acts as the lock. This initial binding event causes the gp120 molecule to undergo a significant change in its three-dimensional shape.
The structural shift in gp120 exposes a previously hidden binding site, allowing it to engage with a second host cell receptor, known as a co-receptor (either CCR5 or CXCR4). This dual binding triggers the irreversible next step of the infection process. Co-receptor engagement destabilizes the entire spike complex, causing the gp120 subunit to move aside.
The newly exposed gp41 subunit then acts as a molecular grappling hook to bridge the gap between the viral envelope and the host cell membrane. The tip of gp41 inserts into the host cell membrane and refolds upon itself, forming a stable structure called a six-helix bundle. This conformational change pulls the two membranes together, forcing them to merge in a process known as membrane fusion. Fusion creates a pore through which the entire conical capsid is delivered directly into the host cell’s cytoplasm.
The Internal Structure and Replication Enablement
Once inside the host cell’s cytoplasm, the conical capsid’s protective structure must remain intact long enough to shield its contents during its initial movement through the cytoplasm. This stability is necessary to ensure the viral payload is not prematurely exposed to the cell’s internal defense mechanisms.
The core contains the viral genome (two copies of single-stranded RNA) and necessary viral machinery, including the enzymes reverse transcriptase and integrase. The protective shell then needs to disassemble in a controlled manner, a process termed “uncoating,” to release its contents at the right time and location. The timing of uncoating is influenced by the action of reverse transcriptase and interactions with host cell proteins.
This controlled breakdown of the capsid structure allows the viral RNA to be converted into a DNA copy by reverse transcriptase. The stability and shape of the conical capsid are mechanisms designed to deliver the replication machinery intact and ensure its activity begins only after successful entry. If the capsid is too stable or breaks apart too quickly, the infection fails.
Structural Targets in Antiviral Therapy
Understanding the HIV virion’s shape and function has provided scientists with precise targets for antiviral drug development. Therapies are designed to interfere with the structural components that enable the virus to execute its life cycle. One major class of drugs, known as fusion or entry inhibitors, specifically targets the external gp120 and gp41 proteins.
Fusion inhibitors work by physically blocking the conformational changes in gp41, preventing the viral and cell membranes from merging. Other entry inhibitors prevent the initial attachment by blocking the binding sites on gp120 or the co-receptors on the host cell surface. These drugs prevent the initial infection from taking hold.
More recently, the conical capsid structure itself has emerged as a promising therapeutic target. Capsid inhibitors are a newer class of drugs that bind to the p24 protein, either stabilizing the capsid so it cannot uncoat or destabilizing it so it breaks apart too early. By disrupting the conical structure, these compounds prevent reverse transcription and the subsequent integration of viral DNA into the host genome.