Cellular tropisms and co‐receptor usage of HIV‐1 isolates from vertically infected children with neurological abnormalities and rapid disease progression

Abstract

The longitudinal evolution of HIV‐1 phenotypes was studied in a cohort of six vertically infected children with early onset and rapid progression of clinical disease. Among 30 viral isolates obtained from peripheral blood, tropisms for both human blood‐derived cells (macrophages, T‐lymphocytes), and for human neural (brain‐derived) cells (microglia, astrocytes) were determined, as was chemokine co‐receptor usage. All children harbored from birth macrophage‐tropic isolates using the CCR5 co‐receptor. Two children later developed T‐cell tropic isolates with CXCR4 and CCR3 usage. While all six patients developed neurological abnormalities, only three produced neural cell tropic isolates, which used CCR5. However, early and persistent finding of both astrocyte‐ and microglia‐tropic isolates in one patient did associate with the most rapid progression to brain atrophy among the six patients. Viral phenotypic properties determined in cell culture did not specifically predict clinical features or course, and the development of AIDS did not coincide with, or depend on, the appearance T‐tropic, syncytia‐inducing viruses. J. Med. Virol. 67:1–8, 2002. © 2002 Wiley‐Liss, Inc.

Quinolinic acid upregulates chemokine production and chemokine receptor expression in astrocytes

“…Inflammation-related production of QUIN (both from monocytic lineage cells within the brain and from astrocytes that have been fed QUIN precursors that are able to cross the blood-brain barrier) leads to an increase of astroglial chemokines and their receptors. These chemokines promote inflammation within the brain and the upregulation of chemokine receptor expression may facilitate HIV infection of astrocytes and microglia (McCarthy et al, 2002). This dynamic and complex interplay between QUIN, astrocyte activation, and chemokines may be directly and/or indirectly involved in the global amplification of inflammatory response within the brain (Coyle and Schwarcz, 2000;Luo et al, 2002).…”

“…Their major involvement in pathogenesis in AIDS is through their function as coreceptors together with CD4 and for brain cell infection by human immunodeficiency virus (HIV) (Gabuzda and Wang, 1999;Boutet et al, 2001;McCarthy et al, 2002).…”

Endocytosis of human immunodeficiency virus 1 (HIV-1) in astrocytes: A fiery path to its destination

“…Interestingly, recent in-vitro study showed protrusions (synapse) from uninfected astrocytes acquiring virus from neighboring HIV-1-infected lymphocytes, but no details on efficiency of viral infection were provided (67). A few studies have suggested some HIV strain selectivity in infecting astrocytes (68–70). However, current knowledge does not explain strain selectivity beyond the major restriction at the viral entry level.…”

“…However, ablating endosomal Rab proteins in astrocytes cripples productive HIV-1 infection, indicating viral entry by endocytosis. A few studies have suggested that there is some HIV-1 strain selectivity in infecting astrocytes efficiently (68,69). However, current knowledge does not explain why astrotropic strain selectivity will occur, given that the brain harbors HIV-1 permissive cells such as microglia and perivascular macrophages.…”

Changes in the HIV Type 1 Envelope Gene from Non-Subtype B HIV Type 1-Infected Children in Kenya

“…17,18 In one study the coreceptor switch of HIV-1 was found in two of six rapid-progressor infants after vertical infection. 19 In another study, 14 of 15 infants with rapid disease progression harbored viruses that used CCR5 as a coreceptor, and only the remaining one had a virus that used both CCR5 and CXCR4.…”