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… - Blood, The Journal of …, 1997 - ashpublications.org
TC Woods, BD Roberts, ST Butera, TM Folks
Blood, The Journal of the American Society of Hematology, 1997ashpublications.org
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 …
Abstract
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.
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