Reports That Describe the Effects of Ex Vivo HIV-1 Infection on Hematopoietic Cells
| Reference . | Method . | Progenitor Growth . | HIV-1 Infection of Progenitors? . | HIV-1 Infection of Clonal Progeny? . | Comments . |
|---|---|---|---|---|---|
| Folks et al173 | HIV-1 challenge of CD34+ BM cells. Infectivity evaluated by RT assay and EM. | Not evaluated. | Evidence of HIV-1 infection at 1 mo pi (RT activity). Virus detected by EM at 40-60 d pi. | Not evaluated. | No convincing evidence of progenitor cell infection. HIV-1–infected CD34+ stromal cells or residual T cells/MΘ could infect differentiating BM cells. |
| Molina et al27 (see Table 2) | Unfractionated BM cells challenged by HIV-1 and seeded into colony assays. | Colony growth normal. | Not evaluated. | No HIV-1 DNA detected (gag PCR). | No evidence of progenitor cell infection. |
| Steinberg et al174 | NATD BM cells and CD34+ BM cells challenged with HIV-1. | ↓ CFU-GM ↓ BFU-E | HIV-1 DNA detected (gag PCR). Signal much weaker in NATD cells. | No HIV-1 DNA detected (gag PCR). | No convincing evidence of progenitor cell infection. Contaminating T cells/MΘ may yield PCR signal. Anti-gp 160 abrogates inhibition of colony growth. |
| Kojouharoff et al175 (see Table 2) | Coculture of CD34+ BM cells with HIV-1-infected M and seeding into colony assays. | Colony growth normal. | Not evaluated. | HIV-1 mRNA transcripts in “40% of CFU-GEMM and CFU-GM (in situ hybridization). | No convincing evidence of progenitor cell infection. MΘ-to-MΘ infection could not be excluded. |
| Zauli et al176 | CD34+ cells from PB infected and seeded into colony assays. | ↓ CFU-GM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | No HIV-1 DNA in pooled colonies (gag PCR). | No evidence of progenitor cell infection. |
| Zauli et al177 | CD34+ BM cells exposed to recombinant gp160, gp120, gp41, & p24. | ↓ CFU-GM & ↓ CD34+ cells via gp160 & gp120. | Not evaluated. | Not evaluated. | Suggests a mechanism for HIV-1-induced cytopenia without direct infection. |
| Calenda et al178 | Challenge of LTBMC with HIV-1 strains LAV and NDK. | ↓↑ CFU-E ↓↑ BFU-E | Virus recovered from LTBMC by cocultured with PBMC. | Not evaluated. | No convincing evidence of progenitor cell infection. Variable results for colony growth (↓↑) depending on virus strain, moi, and time. |
| Steinberg et al8 | Human stromal cell line (BS-1) infected with HIV-1 and cocultured with murine BM progenitors. | ↓ BFU-E ↓ CFU-GM | Not evaluated. Murine lineage cells. | Not evaluated. Murine lineage cells. | Suppression of murine colony growth attributed to HIV-1 infection of stromal cells. |
| Cen et al179 | Challenge of LTBMC and CD34+ BM cells with HIV-1 strains LAV, NL4-3 and ICR 3. | ↓ CFU-GM | No HIV-1 DNA detected (gag/env PCR). | Not evaluated. | No evidence of progenitor cell infection. Treatment of inoculum with anti-gp120 abrogates inhibition of colony growth. Infection of cellular elements in LTBMC with T cell-tropic HIV-1. |
| Zauli et al33 | CD34+ cell line (TF-1) exposed to HIV-1 or gp120 plus anti-gp120 and anti-CD4 antibodies. | Not evaluated. | No viral DNA (gag/env PCR) or protein (p24 ELISA). | Not evaluated. | No evidence of progenitor cell infection. Treatment with gp120 & antibodies induced apoptosis; suggests mechanism for cytopenia. |
| Maciejewski et al167 | Total BM cells, MΘ-depleted BM cells and CD34+ BM cells challenged with HIV-1 or heat-inactivated HIV-1. | ↓ CFU-GM ↓ BFU-E in total BM cultures only. | Not evaluated. | Not evaluated. | Depletion experiments implicate MΘ. Heat-inactivated HIV-1 inhibits colony growth. Inhibition partially blocked by anti-gp120 or anti-TNFα. |
| Schwartz et al180 | BM stroma challenged with HIV-1 strain ADA and overlaid with CD34+ cells. | ↓ CFU-GM ↓ BFU-E | Not evaluated. | Not evaluated. | Factors from HIV-1-infected stroma supress colony growth. Neutralization of IFNα or IL-4 restores growth. |
| Marandin et al61 | Challenge of LTBMC with monocyte-tropic HIV-1. | Colony growth normal. | Not evaluated. | Not evaluated. | MΘ were only infected stromal cells detected. Cytokine profiles unaffected. |
| Chelucci et al21 | CD34+/Lin− PB cells challenged with HIV-1 and seeded into colony assays. | Colony growth normal. | Not evaluated. | HIV-1 DNA (PCR), RNA (RT-PCR) or protein (p24 ELISA) detected. | CFU-GM and BFU-E from PB infected in vitro. CD34+/CD4+ cells (5-20% of total) were presumed targets. |
| Zauli et al172 | CD34+ BM cells challenged with HIV-1 or heat-inactivated HIV-1. | ↓ CFU-GM | No HIV-1 DNA detected (gag PCR). | Not evaluated. | No evidence of progenitor cell infection. gp120 induction of TGFb inhibits colony growth. |
| Kaushal et al181 | CD34+ BM cells (K6.1 MAB selected) challenged with HIV-1. After 24 h reselected for CD34 with ICH3 MAB. | Not evaluated. | No HIV-1 RNA detected (RT-PCR for unspliced and spliced tat-rev-nef transcripts). | Not evaluated. | No evidence of progenitor cell infection. Two-step purification enhances purity of CD34 population. |
| Reference . | Method . | Progenitor Growth . | HIV-1 Infection of Progenitors? . | HIV-1 Infection of Clonal Progeny? . | Comments . |
|---|---|---|---|---|---|
| Folks et al173 | HIV-1 challenge of CD34+ BM cells. Infectivity evaluated by RT assay and EM. | Not evaluated. | Evidence of HIV-1 infection at 1 mo pi (RT activity). Virus detected by EM at 40-60 d pi. | Not evaluated. | No convincing evidence of progenitor cell infection. HIV-1–infected CD34+ stromal cells or residual T cells/MΘ could infect differentiating BM cells. |
| Molina et al27 (see Table 2) | Unfractionated BM cells challenged by HIV-1 and seeded into colony assays. | Colony growth normal. | Not evaluated. | No HIV-1 DNA detected (gag PCR). | No evidence of progenitor cell infection. |
| Steinberg et al174 | NATD BM cells and CD34+ BM cells challenged with HIV-1. | ↓ CFU-GM ↓ BFU-E | HIV-1 DNA detected (gag PCR). Signal much weaker in NATD cells. | No HIV-1 DNA detected (gag PCR). | No convincing evidence of progenitor cell infection. Contaminating T cells/MΘ may yield PCR signal. Anti-gp 160 abrogates inhibition of colony growth. |
| Kojouharoff et al175 (see Table 2) | Coculture of CD34+ BM cells with HIV-1-infected M and seeding into colony assays. | Colony growth normal. | Not evaluated. | HIV-1 mRNA transcripts in “40% of CFU-GEMM and CFU-GM (in situ hybridization). | No convincing evidence of progenitor cell infection. MΘ-to-MΘ infection could not be excluded. |
| Zauli et al176 | CD34+ cells from PB infected and seeded into colony assays. | ↓ CFU-GM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | No HIV-1 DNA in pooled colonies (gag PCR). | No evidence of progenitor cell infection. |
| Zauli et al177 | CD34+ BM cells exposed to recombinant gp160, gp120, gp41, & p24. | ↓ CFU-GM & ↓ CD34+ cells via gp160 & gp120. | Not evaluated. | Not evaluated. | Suggests a mechanism for HIV-1-induced cytopenia without direct infection. |
| Calenda et al178 | Challenge of LTBMC with HIV-1 strains LAV and NDK. | ↓↑ CFU-E ↓↑ BFU-E | Virus recovered from LTBMC by cocultured with PBMC. | Not evaluated. | No convincing evidence of progenitor cell infection. Variable results for colony growth (↓↑) depending on virus strain, moi, and time. |
| Steinberg et al8 | Human stromal cell line (BS-1) infected with HIV-1 and cocultured with murine BM progenitors. | ↓ BFU-E ↓ CFU-GM | Not evaluated. Murine lineage cells. | Not evaluated. Murine lineage cells. | Suppression of murine colony growth attributed to HIV-1 infection of stromal cells. |
| Cen et al179 | Challenge of LTBMC and CD34+ BM cells with HIV-1 strains LAV, NL4-3 and ICR 3. | ↓ CFU-GM | No HIV-1 DNA detected (gag/env PCR). | Not evaluated. | No evidence of progenitor cell infection. Treatment of inoculum with anti-gp120 abrogates inhibition of colony growth. Infection of cellular elements in LTBMC with T cell-tropic HIV-1. |
| Zauli et al33 | CD34+ cell line (TF-1) exposed to HIV-1 or gp120 plus anti-gp120 and anti-CD4 antibodies. | Not evaluated. | No viral DNA (gag/env PCR) or protein (p24 ELISA). | Not evaluated. | No evidence of progenitor cell infection. Treatment with gp120 & antibodies induced apoptosis; suggests mechanism for cytopenia. |
| Maciejewski et al167 | Total BM cells, MΘ-depleted BM cells and CD34+ BM cells challenged with HIV-1 or heat-inactivated HIV-1. | ↓ CFU-GM ↓ BFU-E in total BM cultures only. | Not evaluated. | Not evaluated. | Depletion experiments implicate MΘ. Heat-inactivated HIV-1 inhibits colony growth. Inhibition partially blocked by anti-gp120 or anti-TNFα. |
| Schwartz et al180 | BM stroma challenged with HIV-1 strain ADA and overlaid with CD34+ cells. | ↓ CFU-GM ↓ BFU-E | Not evaluated. | Not evaluated. | Factors from HIV-1-infected stroma supress colony growth. Neutralization of IFNα or IL-4 restores growth. |
| Marandin et al61 | Challenge of LTBMC with monocyte-tropic HIV-1. | Colony growth normal. | Not evaluated. | Not evaluated. | MΘ were only infected stromal cells detected. Cytokine profiles unaffected. |
| Chelucci et al21 | CD34+/Lin− PB cells challenged with HIV-1 and seeded into colony assays. | Colony growth normal. | Not evaluated. | HIV-1 DNA (PCR), RNA (RT-PCR) or protein (p24 ELISA) detected. | CFU-GM and BFU-E from PB infected in vitro. CD34+/CD4+ cells (5-20% of total) were presumed targets. |
| Zauli et al172 | CD34+ BM cells challenged with HIV-1 or heat-inactivated HIV-1. | ↓ CFU-GM | No HIV-1 DNA detected (gag PCR). | Not evaluated. | No evidence of progenitor cell infection. gp120 induction of TGFb inhibits colony growth. |
| Kaushal et al181 | CD34+ BM cells (K6.1 MAB selected) challenged with HIV-1. After 24 h reselected for CD34 with ICH3 MAB. | Not evaluated. | No HIV-1 RNA detected (RT-PCR for unspliced and spliced tat-rev-nef transcripts). | Not evaluated. | No evidence of progenitor cell infection. Two-step purification enhances purity of CD34 population. |
Abbreviations: NATD, nonadherent T-cell depleted; MΘ, macrophage; EM, electron microscopy; PB, peripheral blood; pi, postinfection; LTBMC, long-term bone marrow cultures.