Monocyte maturation, HIV susceptibility, and transmigration across the blood brain barrier are critical in HIV neuropathogenesis.
HIV continues to be a global health crisis with more than 34 million people infected worldwide (UNAIDS: Report on the Global AIDS Epidemic 2010, Geneva, World Health Organization). HIV enters the CNS within 2 weeks of infection and establishes a spectrum of HAND in a large percentage of infected individuals. These neurologic deficits greatly impact the quality of life of those infected with HIV. The establishment of HAND is largely attributed to monocyte transmigration, particularly that of a mature CD14(+)CD16(+) monocyte population, which is more susceptible to HIV infection, across the BBB into the CNS parenchyma in response to chemotactic signals. To enter the CNS, junctional proteins on the monocytes must participate in homo- and heterotypic interactions with those present on BMVECs of the BBB as they transmigrate across the barrier. This transmigration is responsible for bringing virus into the brain and establishing chronic neuroinflammation. While there is baseline trafficking of monocytes into the CNS, the increased chemotactic signals present during HIV infection of the brain promote exuberant monocyte transmigration into the CNS. This review will discuss the mechanisms of monocyte differentiation/maturation, HIV infectivity, and transmigration into the CNS parenchyma that contribute to the establishment of cognitive impairment in HIV-infected individuals. It will focus on markers of monocyte subpopulations, how differentiation/maturation alters HIV infectivity, and the mechanisms that promote their increased transmigration across the BBB into the CNS.
Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY, 10461, USA.
Dionna W
DW
Williams
Eliseo A
EA
Eugenin
Tina M
TM
Calderon
Joan W
JW
Berman
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000821:virology*; D003072:Cognition Disorders / Q000821:virology*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D016130:Immunophenotyping; D008251:Macaca / Q000821:virology; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology