The Human Immunodeficiency Virus (HIV) is a retrovirus, carrying its genetic information in RNA rather than DNA. It targets and gradually weakens the immune system, specifically attacking CD4 cells, a type of white blood cell that helps the body fight off infections. Understanding HIV’s intricate structure provides insight into how it infects cells and how current treatments work to disrupt its lifecycle.
The Outer Shell and Entry Keys
HIV is encased by a viral envelope, an outermost layer derived from the membrane of the host cell it previously infected. Beneath this envelope lies a protein matrix, and further inside, a conical protein shell known as the capsid. The capsid, primarily composed of the p24 protein, encases the virus’s genetic material and enzymes.
Specialized glycoproteins, gp120 and gp41, stud the viral envelope’s surface. The gp120 glycoprotein binds to CD4 receptors and co-receptors (CCR5 or CXCR4) found on the surface of host immune cells. This binding allows the virus to initiate entry into the target cell. Once gp120 binds, it induces changes that facilitate gp41’s interaction, which is responsible for the fusion of the viral and host cell membranes.
The Inner Machinery
Within the capsid lies HIV’s inner machinery: its genetic material and several enzymes. The genetic material consists of two identical strands of single-stranded RNA, which carry all instructions for viral replication. These RNA strands are tightly associated with nucleocapsid proteins, p6 and p7, which help protect them from degradation.
Three essential enzymes are also enclosed within the capsid. Reverse transcriptase converts the virus’s RNA genome into a DNA copy, a unique step for retroviruses. Integrase then inserts this newly synthesized viral DNA into the host cell’s genetic material. The third enzyme, protease, cleaves long viral protein chains into smaller, functional proteins required for new virus assembly.
The Viral Lifecycle
The HIV lifecycle begins with binding, where gp120 glycoproteins attach to CD4 receptors and co-receptors (CCR5 or CXCR4) on a host CD4 cell. This binding triggers gp41 to facilitate fusion of the viral envelope with the host cell’s membrane. Following fusion, the viral capsid and its contents are released into the host cell’s cytoplasm, a process known as uncoating.
Once inside the cytoplasm, reverse transcription occurs. Reverse transcriptase converts the virus’s single-stranded RNA genome into a double-stranded viral DNA molecule. This newly formed viral DNA then moves into the host cell’s nucleus.
Inside the nucleus, the integrase enzyme inserts the viral DNA directly into the host cell’s chromosomal DNA. At this point, the viral DNA is referred to as a “provirus” and becomes a permanent part of the host cell’s genetic material. The host cell’s machinery then begins to treat the proviral DNA as its own, transcribing it into new viral RNA molecules.
Some of these viral RNA molecules serve as the genetic material for new virus particles, while others are translated into long chains of viral proteins. These precursor proteins, along with the newly synthesized viral RNA, then move to the host cell’s membrane for assembly. During assembly, the components gather to form immature virus particles. The final stage, budding and maturation, involves these immature particles pushing out from the host cell, acquiring a piece of the host cell’s membrane to form their outer envelope. During or shortly after budding, the protease enzyme cleaves the long protein chains, transforming the immature virion into a mature, infectious HIV particle.