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HIV: An Immune System Stowaway

By Alex B. Berezow

HIV is generally thought of as a disease of T-cells, specifically ones carrying a particular surface protein called CD4. These CD4+ cells, known as T-helper (TH) cells, are vital to the immune system. One subset, known as TH1, helps macrophages ("large eater" cells) gobble up pathogens, and another subset, known as TH2, helps B-cells produce antibodies. In other words, T-cells act like orchestra conductors, directing and coordinating various aspects of the immune response.

This central role played by TH cells explains why AIDS is such a devastating disease. When HIV infects and destroys them, it leaves the immune symphony without any conductors. In fact, the number of CD4+ cells in the bloodstream is one of the diagnostic criteria for AIDS. A healthy person has 500-1000 CD4+ cells per microliter of blood; a person with AIDS has fewer than 200.

Unfortunately for our immune systems, TH cells aren't the only ones susceptible to HIV infection. Dendritic cells, which are sort of like police officers patrolling the streets, can also become infected*. Even worse, once they are infected, they can directly transmit the virus to TH cells. (See micrograph.)

A dendritic cell (left) is in contact with a T-cell (right). Notice the yellow blob (which is actually in the dendritic cell). That yellow color is produced by a merger of two colors: A particular dendritic cell receptor, called Siglec-1 (labeled green) and HIV particles (labeled red). The receptor binds the HIV particles. (Green + Red = Yellow) When the dendritic cell makes contact with the T-cell, the receptors head toward the T-cell, dragging along HIV particles with them. This cell-to-cell contact then transfers the virus from the dendritic cell to the T-cell.

Of course, the dendritic cell is not purposefully infecting the T-cell; HIV has hijacked this normal cell receptor for a more nefarious purpose. Indeed, HIV is a stealthy stowaway.

*Update (1/25/13 @ 1:46 pm PST): A point of clarification: The mature dendritic cell is not productively infected, which means it does not produce more virus particles. Instead, it simply captures HIV and shuttles it to the T-cell.

Source: Izquierdo-Useros N, Lorizate M, Puertas MC, Rodriguez-Plata MT, Zangger N, et al. (2012) Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides. PLoS Biol 10(12): e1001448. doi:10.1371/journal.pbio.1001448

Source: Sedwick C (2012) How HIV Sneaks aboard Mature Dendritic Cells. PLoS Biol 10(12): e1001454. doi:10.1371/journal.pbio.1001454

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