Increased susceptibility of neonatal monocyte/macrophages to HIV-1 infection.
The relative susceptibility of neonatal/cord blood monocyte/macrophages to productive infection with human immunodeficiency virus type 1 (HIV-1) was investigated. In addition, the effect of HIV-1 infection of cord blood monocyte/macrophages in various stages of maturation/differentiation as represented by differing ages of monocytes in culture was examined. Monocyte/macrophages were infected with two viral strains isolated and cloned from primary clinical isolates, each with different cell tropisms. Cord blood and adult monocyte/macrophages were infected with either the macrophage-tropic strain HIV-1(JR-FL) or the predominantly lymphocyte-tropic strain HIV-1(JR-CSF). p24gag antigen levels were measured in supernatants by ELISA. Cord monocyte/macrophages at three different ages in culture (4, 7, and 11 days) were more productively infected by both viral strains than were adult monocyte/macrophages infected in parallel. In addition, the less differentiated cells (cord and adult monocyte/macrophages infected after growing 4 days in culture) were more productively infected than were the more differentiated monocyte/macrophages (cells infected after growing 7 or 11 days in culture). The mechanism for this increased susceptibility of cord monocyte/macrophages to HIV-1 infection as compared to adult cells was also investigated. A measurable increase in DNA synthesis was found in the infected cord cells when compared to infected adult cells and to uninfected adult or cord cells as represented by increased [3H]thymidine incorporation, suggesting that increased cell proliferation of cord monocyte/macrophages may enhance the permissivity of infection. This article suggests that cord monocyte/macrophages may play an important role in the pathogenesis of perinatal HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)
Sperduto
A R
AR
Department of Pediatrics, UCLA School of Medicine 90024.
Bryson
Y J
YJ
Chen
I S
IS
D000328:Adult; D000367:Age Factors; D002454:Cell Differentiation; D002455:Cell Division; D005312:Fetal Blood / Q000166:cytology / Q000382:microbiology; D015658:HIV Infections / Q000097:blood / Q000209:etiology* / Q000382:microbiology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007700:Kinetics; D008264:Macrophages / Q000382:microbiology / Q000473:pathology; D009000:Monocytes / Q000382:microbiology / Q000473:pathology; D014779:Virus Replication