Does reduced DNA repair capacity play a role in HIV infection and progression in the lymphocytes of opiate addicts?
Opiate use in vivo and in vitro reduces the ability of human peripheral lymphocytes to repair DNA damage caused by both the physical and chemical mutagens that produce single-strand adducts. This decrease in repair leads to increased genetic damage to the individual cell as measured by cytogenetic damage, including sister chromatid exchanges and formation of micronuclei. The expected consequences of this increase in damage can also be established by increases in host cell mutation rate and rate of apoptosis. The effect of this increase in genetic damage can be expected to have significant consequences for HIV-1 or simian immunodeficiency virus infecting those lymphocytes. For example, DNA damaging agents have long been known to induce lentiviral growth and propagation, and this has been found to be true for HIV-1 following ultraviolet light treatment of lymphocytes. However, to date, no one has fully explored the consequences of increased host mutation rate on HIV growth and maintenance. Recent reports have demonstrated the role of viral mutation in such key physiologic processes as resistance to highly active antiretroviral therapy (HAART). Beyond the effects of random mutations in the viral genome, specific mutations in the HIV-1 transcriptase and protease lead to increased accumulation of mutant viruses and the gradual failure of HAART. It therefore remains to be tested whether changes in host cell mutation rate will also predict changes in susceptibility to drug therapy. This also leads to questions about whether the higher rate of viral mutation in HIV-infected drug addicts might be the basis for higher rates of neuroAIDS in this population. It would be attractive to speculate that the increase in the heterogeneity of the virus in addicts produces mutants with a greater capacity to attack neuronal tissue and a high affinity to replicate there.
Madden
John J
JJ
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA. jjmadden@mindspring.com
Wang
Yichong
Y
Lankford-Turner
Pamela
P
Donahoe
Robert M
RM
D003042:Cocaine / Q000494:pharmacology; D004260:DNA Repair; D015658:HIV Infections / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D003932:Heroin / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects / Q000821:virology; D009020:Morphine / Q000494:pharmacology; D009154:Mutation; D009294:Narcotics / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000150:complications*; D014466:Ultraviolet Rays
D009294:Narcotics; D003932:Heroin; D009020:Morphine; D003042:Cocaine