Loss of inducible virus in CD45RA naive cells after human immunodeficiency
virus-1 entry accounts for preferential viral replication in CD45RO memory
cells
TC Woods, BD Roberts, ST Butera and TM Folks
Retrovirus Diseases Branch, Centers for Disease Control and Prevention,
Atlanta, GA 30333, USA.
Controversy exists concerning the preferential infection and replication of
human immunodeficiency virus-1 (HIV-1) within naive (CD45RA+) and memory
(CD45RO+) subsets of CD4+ lymphocytes. To explore the susceptibility of
these subsets to HIV-1 infection, we purified CD45RA+/CD4+ (RA) and
CD45RO+/CD4+ (RO) cells from normal donors and subjected them to a novel
monokine activation culture scheme. Following HIV-1 infection and
interleukin-2 (IL-2) induction, viral production measured on day 13 was
19-fold greater in RO cultures compared with RA cultures. IL-2-stimulated
proliferation in uninfected control cultures was equivalent. To explore the
mechanisms by which RA cells were reduced in viral production capacity, RA
and RO cells were exposed to HIV-1 followed by treatment with trypsin, and
then phytohemagglutinin antigen (PHA)-stimulated at days 4, 7, and 10
postinfection. HIV-1 production in day 4 postinfection RA and RO cultures
was analogous, indicating that viral fusion and entry had occurred in both
cell types. However, whereas similarly treated day 7 and 10 postinfection
RO cultures produced virus, HIV-1 was markedly reduced or lost in the
corresponding RA cultures. These results suggest that a temporally labile
postfusion HIV-1 complex exists in unstimulated RA cells that requires
cellular activation signals beyond that provided by IL-2 alone for
productive infection.
Volume 89,
Issue 5,
pp. 1635-1641,
03/01/1997
Copyright © 1997 by The American Society of Hematology
