Implications of Chronic Alcoholism for HIV Infection

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Alcohol dependence is the most common form of drug abuse in the US, with around 7% of the population meeting criteria for alcoholism (Grant 1994). We all know that the effects of alcohol are wide-ranging, impacting both behavior and physiology; it impairs judgement, motor skill, etc. It has been known to weaken the immune system, and research in the past few years has linked the effects of alcohol to HIV infection. Common sense tells us that alcohol promotes risky behaviors, including those that increase the possibility of HIV infection (sex, drugs, etc.). Recent interest in binge drinking and HIV has produced data showing alcohol in a binge pattern changed the proportion of immune cells after SIV infection in rhesus macaques, a common animal model for HIV, and may even increase the disease course (Molina et al 2006, Poonia et al 2006). But researchers at the Scripps Research Institute have also showed that chronic alcoholism may generate microenvironments in the body that are more vulnerable to HIV infection.

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To accomplish this study, the researchers developed a protocol in which rhesus macaques self-administered alcohol orally, twice a day for 30 days before infection and during infection. To do this, they mixed alcohol and an orange flavored drink in different ratios, and conditioned the animals to drink the solution (replacing water with the alcohol solution for a short duration). The final concentration given to the animals was 6% alcohol, similar to the alcohol content of most beers, and animals drank enough alcohol per day to cause blood alcohol levels that in humans are greater than the legal driving limit and would decrease motor skill. When the animals were conditioned, they were infected with SIVmac251, a strain of SIV that induces high peak and steady viral loads and is also known to infect the CNS (Burdo et al 2005). SIVs, simian immunodeficiency viruses, are retroviruses that infect non-human primates and produces symptoms and changes in physiology that mirror those induced by HIV infection (it is generally believed that HIV originated from SIV crossing the species barrier to humans).

Breaching the Great Wall: Attack of the Immune Cells on the Central Nervous System

The brain is considered the most complex living structure known in the universe. This organ is responsible for controlling all bodily functions ranging from heart rate to motor functions. Given the complexity and importance of the brain, it is vital that proper defenses are maintained, one of which is the blood brain barrier. The blood brain barrier (BBB), as the name implies, serves as an anatomical barrier against invading pathogens by blocking their entry into the brain. Think of it as the Great Wall of China that was built in order to protect the Chinese empire against invasion by nomadic tribes. In this analogy, the brain would be considered the Chinese empire. Similar to the bricks and stones making up the Great Wall, tight junctions present between the endothelial cells of the blood vessels make up the BBB and they function to allow passage of only certain molecules such as oxygen. Even molecules such as glucose must undergo an active transport mechanism in order to pass through the BBB. The central nervous system (CNS) is considered an immunoprivileged organ in that CNS antigens are not accessible to immune cells in the periphery. Likewise, peripheral immune cells and pathogens cannot easily penetrate the BBB.

During the course of various neurological diseases such as multiple sclerosis (MS), vascular dementia, and stroke, this great wall becomes compromised thereby triggering the infiltration of immune cells into the CNS. This process in turn causes inflammation. Studies on animal models of these diseases aim to unravel the mechanisms by which certain immune cells breach the BBB (Simka, 2009). Unraveling such mechanisms provides therapeutic targets for future investigations in the hope of finding an effective treatment.