Grouppe Kurosawa: HIV - The Enhancing Effects of Physical and Psychology Stress on HIV Infectivity (print)

The Enhancing Effects of Physical and Psychology Stress on HIV Infectivity

NEF, TAT, and REV are viral regulatory proteins that are synthesized in infected cells before viral structural proteins, such as GAG and GP160. It is often under appreciated that the HIV virus infects human beings, and human beings are complicated organisms. In the presence of chronic stress, any pathogen can become established in the body because the immune response to varying extents becomes immunosuppressed. The concept of the "sickly" child or adult is well documented in the psychiatric literature and is usually traced to the inability of an individual to avoid psychological stress. For example, some people develop colds all the time, although changes in environmental temperatures have nothing to do with susceptibility to viral infections. Since most periods of psychological or physical stress are limited in duration, the immune response naturally regenerates itself and the pathogen is eventually cleared. This is clearly not the case with an HIV infection. The virus itself is intrinsically immunosuppressive and not solely because it infects T lymphocytes and macrophages. When exposure to the HIV virus parallels exposure to stress, the combination is very likely to be inherently fatal. Recreational drugs such as opiates, amphetamines, cocaine, binge drinking and nitrite inhalants (poppers) all cause substantial stress. In addition to activating the hypothalamic-pituitary-adrenal axis, drugs such as morphine and cocaine cause various specific immune dysfunctions, which transcend their ability to increase the level of hydrocortisone in the blood. Surgical procedures requiring blood transfusions are extremely stressful as are burns, hemorrhages, and childbirth. Malnutrition and the presence of chronic infections associated with poverty are also stressful. The rapid spread of AIDS amongst homosexuals may be directly linked to the high incidence hepatitis B/C, cytomegalovirus, syphilis, gonorrhea, chlamydia, gay bowel syndrome, anal fissures and papilloma virus infections common in the gay community. Stressors, whether physical or psychological, are all around us, but the presence of HIV, at least up until this point, is not. If a person was under stress when exposed to the HIV virus, their CD8 T cells and macrophages might not be able to make the RANTES and MIP-1 immune hormones necessary to inhibit the spread of the virus. As the viral titer increases, so does the synthesis of VPR, TAT and NEF, which further contributes to the immune dysfunction associated with a stress related immunosuppression. Of course, glucosteroids are immunosuppressive in more ways than merely inhibiting the synthesis of RANTES and MIP-b 1/2. It is also important to remember that being diagnosed as HIV positive is currently considered a death sentence, the availability of drug cocktails notwithstanding. This knowledge, in and of itself, must generate a tremendous amount of psychological stress. Numerous psychological studies have found that stressful life events are more predictive of disease progression than the number of sexual experiences. It would be a tragic irony if the psychological stress of a positive HIV diagnosis contributed to the progression of the disease, thereby creating a self-fulfilling prophesy equating infection with inevitable death. It is interesting that a very high percentage of long term survivors of HIV infections are hemophiliacs, people who were exposed to the HIV virus in the relative absence of stress.

Stress is adaptive when induced to limit the spread of pro-inflammatory hormones released during bacterial or viral infections. Under these conditions, hydrocortisone is not immunosuppressive, because the previously released immune hormones modulate its activity. However, if the stress is caused by a burn, the high hydrocortisone levels in the blood can inhibit cellular immunity, which makes burn patients very susceptible to infections. Stress does not cause AIDS. It may contribute to the dissemination of HIV throughout the lymphatic system, but it also largely confines the infection to those organs. AIDS does not develop until the virus and virally infected cells invade other tissues. This occurs when pro-inflammatory hormones such as TNF and IL-1 are increasingly released in response to high viral titers and the presence of opportunistic infections. The steroid resistance these hormones induce, even in the presence of elevated concentrations of hydrocortisone, allows pro-inflammatory hormones to ravage every tissue in the body without constraint. In a normal viral infection, that constraint would be the activation of the stress response. At this late point in the HIV infection, however, the stress response no longer functions because the cells in each tissue of the body are increasingly resistant to hydrocortisone's anti-inflammatory properties. It is paradoxical that the collapse of the glucosteroid/TGFb-mediated immunosuppression, the physiological event that characterizes the asymptomatic period of infection, may actually be responsible for "triggering" the development of the clinical syndrome we call AIDS