Retroviruses & What Makes HIV So Deadly?

Retroviruses used to be called “RNA tumor viruses” because many induce tumors in animals (only very rarely in humans). Now, of course, retroviruses are more familiar because the HIV virus, which causes AIDS, is a retrovirus. It should be noted that most retroviruses do NOT kill cells, and the consequences of a retroviral infection are generally benign. HIV is an exception.

Structure of HIV. The two copies of the viral RNA are protected by a protein coat and enclosed in a capsule. Also contained in the capsule are reverse transcriptase enzymes (which convert the single-stranded RNAs into double-stranded DNA copies), integrase (which inserts the DNA version into the host genome), and protease (which cuts the long chain of polypeptides produced by viral RNA into individual enzyme components as new virus particles are budding off a cell membrane). The capsule is itself enclosed in a bilayer membrane obtained from the previous host cell; in the membrane are mounted P17 (the remains of a protein involved in budding off) and GP120 (the glycoprotein that binds the helper T-cell receptor and so enables the virus to gain entry into its host).

Structure of a Retrovirus

• Genome:2 identical copies of RNA, each has about 10,000 base pairs
• Internal structural proteins: one layer is associated with the outer membrane, the inner layer binds to the RNA molecules, and the middle layer forms the coat, or capsid.
• Viral enzymes: Three in general: Reverse transcriptase, integrase, and a protease.
• Lipid membrane: bilipid layer around the outside, derived from the host cell.
• Viral surface proteins: there are around 200 molecules that can attach to specific cellular receptors on the host cell.

Retrovirus Life Cycle

1. Attachment and entry: The viral surface proteins bind to specific receptor protein(s) (e.g., for HIV, CD4 + one other) on the surface of the host cytoplasmic cell membrane. The interaction causes the membrane of the virus and the host cytoplasmic membrane to fuse and the RNA and viral enzymes are released inside the cell.
2. Synthesis of double-stranded cDNA from RNA using the enzyme reverse transcriptase.
3. Transport of cDNA to the nucleus. The nuclear membrane presents a barrier. Many retroviruses go in during mitosis when the membrane breaks down; others (like HIV) require a special mechanism to get through the pores.
4. Integration of the cDNA into the genome, catalyzed by integrase. The cDNA inserts at random sites in host chromosomes. Once integrate it is called a provirus and unlike a lysogenic phage, it never comes out. The viral DNA becomes a permanent addition to the genetic repertoire of the host cell.
5. Gene Expression: The host cell machinery transcribes the viral DNA.
6. Protein synthesis of the various viral proteins occurs using the host cell ribosomes.
7. Assembly. The viral RNAs and viral proteins aggregate on the cell membrane, and the membrane begins to bud.
8. Maturation. The viral protease enzyme cuts the structural proteins into defined segments and activates the enzymes destined to be packaged with the virus, as well as the proteins of the capsid. Once the capsid is formed, the virus buds off and is free to bind to another host cell.

Why is HIV So Deadly?

The HIV virus specifically recognizes and binds to the cell surface CD4 receptor protein on the membrane of host cells. CD4 receptors are found on certain cells of the lymphatic system, particularly one class of T lymphocytes, the helper T cells. Some human brain cells and intestinal cells can also be infected with HIV. There are two features of HIV that make it particularly deadly:

HIV eventually kills the helper T cells it infects rather than living in symbiosis with them, as do most retroviruses. Helper T cells are vitally important in defending us against infection. The integrated viral DNA (provirus) becomes a permanent addition to the chromosome and persists in a latent state until some unknown event activates it and replication begins. Antiviral drugs cannot be used to treat the infection while the provirus is hidden away in a chromosome.

Infection of a cell by a retrovirus. (A) A retrovirus enters a host cell by a type of endocytosis. (B) Inside the cell the protein coat is stripped off, and viral RNA (red) is released into the cytoplasm. The reverse transcriptase that is carried by the virus then catalyzes the formation of a cDNA copy (green) of the viral RNA. (C) The cDNA copy then moves to the nucleus where it is incorporated as a provirus into one of the host cell chromosomes (blue). The provirus functions as part of the chromosome and codes for viral proteins (brown). (D) The provirus is replicated along with the host chromosomes when the host cell divides and is passed on to the daughter cells.

How AIDS takes over

The AIDS virus is a retrovirus, which means that instead of storing its genetic program in DNA, as most viruses do, it uses RNA. And though the AIDS virus is frail outside the body, it’s remarkably immune to drugs once it’s inside. That’s because it can reproduce a key component of its host cell’s genetic machinery. This phenomenon, which isn’t seen in other retroviruses, is called TAT, and it speeds up the reproduction of the AIDS virus, a process that ultimately allows it to destroy the body’s immune system.

Download Printable (PDF) Version

Back to Main Menu / Previous Objective / Next Objective /