Macrophage-HIV interaction: viral isolation and target cell tropism.
Viral isolates were recovered by cocultivation on macrophage colony-stimulatingfactor (MCSF)-treated monocyte target cells from peripheral blood mononuclear cells (PBMCs) in 25 out of 27 patients seropositive or at risk for HIV infection. Frequency of virus recovery was independent of the patient's age, sex, numbers of CD4+ T cells, clinical stage or zidovudine (azidothymidine) therapy. Sixteen out of 19 HIV isolates were serially passaged in MCSF- treated monocytes. Five out of five virus isolates were also passaged in phytohemagglutinin/interleukin-2 (PHA/IL-2)-treated lymphoblasts. In lymphoblasts, no qualitative or quantitative differences were observed between these isolates and human T-cell leukemia virus IIIB (HTLV-IIIB) for (1) release of p24 antigen reverse transcriptase, and infectious virus, (2) induction of typical cytopathic effects (cell syncytia in 3-10% of cells) and cell lysis, (3) frequency of infected cells (5-20% of PBMC) as detected by in situ hybridization for HIV RNA, (4) down-modulation of T cell plasma membrane CD4, and (5) site of progeny virion assembly and budding (plasma membrane only with no intracytoplasmic accumulation of virus). Progeny virus recovered from infected lymphoblasts was fully infectious for other lymphoblasts, but failed to infect MCSF-treated monocytes. Detailed analysis of target cell tropism among HIV isolates showed that HIV isolated in monocytes infected both monocytes and lymphoblasts; progeny virus isolated in lymphoblasts infected only T cells. HIV interacts differently with monocytes and T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention.
Gendelman
H E
HE
Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland.
Baca
L M
LM
Husayni
H
H
Turpin
J A
JA
Skillman
D
D
Kalter
D C
DC
Orenstein
J M
JM
Hoover
D L
DL
Meltzer
M S
MS
D000328:Adult; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005260:Female; D015683:Gene Products, gag / Q000302:isolation & purification; D006678:HIV / Q000302:isolation & purification*; D016655:HIV Core Protein p24; D006679:HIV Seropositivity / Q000382:microbiology*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000382:microbiology; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D014758:Viral Core Proteins / Q000302:isolation & purification
D003115:Colony-Stimulating Factors; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D007376:Interleukin-2; D010835:Phytohemagglutinins; D014758:Viral Core Proteins; D016173:Macrophage Colony-Stimulating Factor