Route and susceptibility: mucous membranes and target cells

HIV is only able to infect certain specific cells – those that display CD4 protein on their surface. While this clearly includes CD4 cells themselves, other blood cells such as macrophages and CD8 cells are also susceptible to infection, as are specific cells in the lungs, the brain, the gastrointestinal tract and the kidneys.

HIV can only be transmitted and cause infection if it gets into the body via a route where these vulnerable cells are plentiful. Intact, undamaged skin forms a very effective barrier to infection, as skin itself contains no cells that are susceptible to HIV infection. For infection to occur, the virus must enter the body directly via the bloodstream, or via the mucous membranes.

Blood-to-blood transmission (such as through shared needles) is clearly a highly efficient route of infection, since infected cells and/or cell-free virus in the infected person's bloodstream gain direct access to the other person's bloodstream, which is laden with susceptible cells. Damaged or wounded skin forms another possible means of circumventing the barrier of the skin and gaining access to the body.

However, direct access to the bloodstream is not necessary for infection to occur: the mucous membranes of the body provide another vulnerable route. Mucous membranes are the moist membranes lining body cavities that are not protected by skin: this includes the mouth and oesophagus, the nostrils, the eye sockets, and the rectum. Genital areas covered by mucous membranes include the vagina, the urethra, and the underside of the foreskin.

Mucous membranes, such as those in the genitals and rectum, are susceptible to forms of damage through which HIV can enter – including larger-scale tissue damage leading to bleeding, minute abrasions, and tissue damage from ulcerative sexually transmitted infections such as herpes.

However, this type of damage is not needed for infection to occur. Mucous membranes also contain large numbers of cells called dendritic cells. Dendritic cells (including a subset known as Langerhans cells) are in fact designed precisely to ‘ferry’ infectious particles to the lymph nodes. There, they act as antigens that stimulate the immune response. However, as HIV specifically targets and infects activated immune cells, it is able to exploit this normally protective activity. While routing other pathogens to the lymph nodes allows the immune system to target and destroy them, HIV is given broad access to precisely the activated immune cells that it most readily infects.

Dendritic cells do not necessarily need to become infected with HIV themselves in order to transport HIV further into the body. The virus’s gp120 envelope protein can also attach itself to a ‘sticky’ molecule called DC-SIGN which coats the dendritic cells. Either way, HIV is given a route by which it can travel through mucosal membranes into deeper tissue areas rich in macrophages and activated T-cells, where it can establish itself and from there can spread throughout the immune system.