HIV Structures and Life Cycle
HIV Structures and Life Cycle
HIV consists of a cylindrical center surrounded by a sphere-shaped lipid bilayer envelope (Figure 9.2). There are two major viral glycoproteins in this lipid bilayer, gp120 and gp41. The major function of these proteins is to mediate recognition of CD4+ cells and chemokine (cytokine) receptors, thereby enabling the virus to attach to and invade CD4+ cells. The inner sphere contains two single-stranded copies of RNA, as well as multiple proteins and enzymes necessary for HIV replication and maturation: reverse transcriptase, integrase, and protease. Unlike other retroviruses, HIV uses nine genes to code for the necessary proteins and enzymes.
HIV's Life Cycle
Host cells infected with HIV have a shortened life span as a result of the virus's using them as "factories" to produce multiple copies of new HIV. Thus, HIV continuously uses new host cells to replicate itself. As many as 10 million to 10 billion virions (individual viruses) are produced daily. In the first 24 h after exposure, HIV attacks or is captured by dendritic cells in the mucous membranes and skin. Within 5 days after exposure, these infected cells make their way to the lymph nodes and eventually to the peripheral blood, where viral replication becomes rapid. CD4+ lymphocytes that are recruited to respond to viral antigen migrate to the lymph nodes. These become activated and then proliferate via complex interaction of cytokines released in the microenvironment of the lymph nodes. This sequence of events makes the CD4+ cells more susceptible to HIV infection, and it explains the generalized lymphadenopathy characteristic of the acute retroviral syndrome seen in adults and adolescents. In contrast, HIV-infected monocytes allow viral replication but resist killing. Thus, monocytes act as reservoirs of HIV and as effectors of tissue damage in organs such as the brain.
The HIV life cycle includes six phases: binding and entry, reverse transcription, integration, replication, budding, and maturation.
Binding and Entry: The envelope proteins gp120 and gp41 bind to CD4+ cell receptors and coreceptors on the outside of CD4+ cells and macrophages. The chemokine receptors facilitate viral entry. The joining of the proteins and the receptors and coreceptors fuses the HIV membrane with the CD4+ cell membrane, and the virus enters the CD4+ cell and macrophage. The HIV membrane and the envelope proteins remain outside of the CD4+ cell, whereas the core of the virus enters the CD4+ cell. CD4+ cell enzymes interact with the viral core and stimulate the release of viral RNA and the viral enzymes reverse transcriptase, integrase, and protease.
Reverse Transcription: The HIV RNA must be converted to DNA before it can be incorporated into the DNA of the CD4+ cell. This incorporation must occur for the virus to multiply. The conversion of HIV RNA to DNA is known as reverse transcription and is mediated by the HIV enzyme reverse transcriptase. The result is the production of a single strand of DNA from the viral RNA. The single strand of this new DNA then undergoes replication into double-stranded HIV DNA.
Integration: Once reverse transcription has occurred, the viral DNA can enter the nucleus of the CD4+ cell. The viral enzyme integrase then inserts the viral DNA into the CD4+ cell's DNA. This process is known as integration. The CD4+ cell has now been changed into a factory used to produce more HIV.
Replication: It is the process of making replica (copy). The new DNA, which has been formed by the integration of the viral DNA into the CD4+ cell, causes the production of messenger DNA that initiates the synthesis of HIV proteins.
Budding: It is a form of asexual reproduction in which a new organism develops from an outgrowth or bud on another one. The HIV proteins and viral RNA, all the components needed to make a new virus, gather at the CD4+ cell membrane to form new viruses. These new viruses push through the different parts of the cell wall by budding. Many viruses can push through the wall of one CD4+ cell. These new viruses leave the CD4+ cell and contain all the components necessary to infect other CD4+ cells.
Maturation: The new virus has all the components necessary to infect other CD4+ cells but cannot do so until it has matured. During this process, the HIV protease enzyme cuts the long HIV proteins of the virus into smaller functional units that then reassemble to form a mature virus. The virus is now ready to infect other cells.