Reports That Describe Hematopoietic Function of Cells Obtained From HIV-1–Seropositive Patients
| Reference . | Method . | Progenitor Growth . | HIV-1 Infection of Progenitors? . | HIV-1 Infection of Clonal Progeny? . | Comments . |
|---|---|---|---|---|---|
| Stella et al40 | BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-GEM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | Not evaluated. | Depletion of T cells enhanced colony growth. Suggest a T-cell imbalance may contribute to impaired hematopoiesis. |
| Donahue et al182 | BM cells from HIV-1+patients seeded into colony assays in the presence/absence of anti–HIV-1 antisera. | ↓ CFU-GM & ↓ BFU-E only in presence of antisera. | Not evaluated. | HIV-1 in pooled colonies from 1/4 patients (RT activity in culture supernatants). | No convincing evidence of progenitor cell infection. More differentiated cells in culture may be virus source. Anti-gp120 antibodies may be suppressive elements in patient sera. |
| Lunardi-Iskandar et al11 | BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | Not evaluated. | Not evaluated. | Depletion of adherent cells or T cells or addition of cytokines (GM-CSF, IL-3, Epo) did not restore colony growth). |
| Molina et al27 (see Table 1) | BM cells from HIV-1+ patients seeded into colony assays. | Colony growth normal. | Not evaluated. | No HIV-1 DNA detected (gag PCR). | No evidence of progenitor cell infection. Propose cytopenias due to alteration in BM microenvironment. |
| Von Laer et al183 | Culture of purified CD34+ BM cells from HIV-1+ patients. | Not evaluated. | HIV-1 DNA detected in 1/14 samples (gag PCR). | Not evaluated. | No convincing evidence of progenitor cell infection. Single positive attributed to CD4+ T-cell contamination. |
| Ganser et al184 | BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-GEM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | No HIV-1 detected (immunohistochemistry and in situ hybridization). | No evidence of progenitor cell infection. |
| Davis et al28 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-E | HIV-1 DNA detected in 1/11 samples (gag/env PCR). | No HIV-1 DNA detected (gag/env PCR). | No convincing evidence of progenitor cell infection. Single positive attributed to CD4+ T-cell or MΘ contamination. |
| Kojouharoff et al175 (see Table 2) | BM cells from HIV-1+ patients seeded into colony assays. | Colony growth normal. | Not evaluated. | HIV-1 mRNA detected in CFU-GEM & CFU-GM in 2/6 patients (in situ hybridization) | No convincing evidence of progenitor cell infection. HIV-1+ cells may reflect infection of a more differentiated phenotype. |
| Zauli et al25 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-E ↓ CFU-Mk | No HIV-1 DNA (gag PCR) or protein (p24 ELISA) detected. | Not evaluated. | No evidence of progenitor cell infection. HIV-1 detected in unfractionated bone marrow samples. A role for HIV-1 in the BM microenvironment proposed. |
| Zauli et al185 | Purified CD34+ BM cells from HIV-1+patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-Mk | HIV-1 DNA detected in 2/17 samples (gag/env PCR). No p24 in culture supernatants. | Not evaluated. | No convincing evidence of progenitor cell infection. Two positives attributed to CD4+ T-cell or MΘ contamination. 9 CFU-Mk in all samples implies an indirect mechanism. |
| Stanley et al150 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | HIV-1 DNA (gag/env PCR) & virus (co-culture) detected in 17/52 & 8/29 Zairian and 3/22 & 1/2 American samples. | Not evaluated. | HIV-1 detected only in subset of patients with advanced disease. 9 CFU-GM & 9 BFU-E in all samples implies an indirect mechanism. CD34+ accessory cells are potential source of HIV-1. |
| Louache et al186 | BM cells from 27 HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | No HIV-1 DNA detected (gag PCR). | No evidence of progenitor cell infection. Anti-sense nef or tat increased clonal growth. |
| Kaczmarski et al187 | BM cells from HIV-1+ patients studied in LTBMC and colony assays. | Normal CFU-GEMM and CFU-GM. | Not evaluated. | HIV-1 DNA detected in pooled CFU-GEMM, CFU-GM & CFU-LTC (gag/env/tat PCR). | No convincing evidence of progenitor cell infection. No T-cell depletion so infection of differentiating cells could not be ruled out. |
| De Luca et al29 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | No HIV-1 DNA detected (gag PCR). | Not evaluated. | No evidence of progenitor cell infection. |
| Hillyer et al7 | Purified CD34+ cells from SIV-infected macaques seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | No SIV DNA detected (gag PCR). | SIV DNA detected in occasional pooled CFU-GM colonies. | No convincing evidence of progenitor cell infection. Rare positive signal attributed to CD4+ T-cell or MΘ contamination. |
| Neal et al34 | Purified CD34+ BM cells from HIV-1+ patients studied in LTBMC and colony assays. | Normal CFU-E, BFU-E, CFU-GM & cobblestone formation in LTBMC. | HIV-1 DNA detected in 2/10 patients (gag/pol PCR). | All pooled CFU-GM were HIV-1 DNA negative (gag/pol PCR). 1/5 pooled CFU-E/BFU-E were weakly HIV-1+ (<2 copies/75,000 cells). | No convincing evidence of progenitor cell infection. Low proviral DNA copy number in pooled colonies (2-5 copies/250,000 cells) suggests (CD4+ T-cell or MΘ contamination. |
| Dallalio et al188 | Purified CD34+ BM cells from 5 HIV-1+ patients seeded into CFU-E assays | Normal CFU-E. | Not evaluated. | Not evaluated. | CFU-E were not more sensitive to cytokine-mediated inhibition of colony formation. |
| Slobod et al31 | Mobilization of CD34+ BM cells from HIV-1+ patients. Nested PCR for evidence of HIV-1 infection. | Not evaluated. | HIV-1 DNA in 2/7 patients but in only 1/3 replicate samples (nested env PCR detecting 1 DNA copy/25,000 cells). | Not evaluated | No convincing evidence of progenitor cell infection. CD34+ cells at 92-99% purity so variable positives attributed to CD4+T-cell contamination. |
| Marandin et al189 | Primitive BM cells from HIV-1+ patients evaluated by flow cytometry. Fractionated CD34+ cells studied in LTBMC and colony assays. | ↓ CFU-GM ↓ BFU-E ↓ LTC-IC | No HIV-1 DNA detected (gag PCR). Included separate analysis of CD34+/CD4+, CD34+/CD38+ & CD34+/CD38− populations. | No HIV-1 DNA detected (gag PCR). | No significant change in percentage of CD34+ cells in HIV-1+ patients but proportions of CD34+/CD38− & CD34+/Thy 1+ cells decreased. Suggests loss of more primitive phenotype but not via direct infection. |
| Kearns et al151 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM | HIV-1 DNA detected in rare samples. Semi-quantitative PCR estimates 1/100,000 cells infected. | Not evaluated. | No evidence of significant progenitor cell infection. Propose dysregulated hematopoiesis due to alterations in the BM microenvironment. |
| Bahner et al52 | Ex vivo infection of human marrow stromal cells with HIV-1 and stomal cells genetically modified to resist HIV-1 infection. Stroma overlayered with bone marrow cells. | ↓ CFU-GM (obtained after 3 wk on stroma) | Not evaluated. | Not evaluated. | Stroma is infectable. Reduced capacity of HIV-1-infected stroma to support hematopoietic progenitor cell growth. |
| Reference . | Method . | Progenitor Growth . | HIV-1 Infection of Progenitors? . | HIV-1 Infection of Clonal Progeny? . | Comments . |
|---|---|---|---|---|---|
| Stella et al40 | BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-GEM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | Not evaluated. | Depletion of T cells enhanced colony growth. Suggest a T-cell imbalance may contribute to impaired hematopoiesis. |
| Donahue et al182 | BM cells from HIV-1+patients seeded into colony assays in the presence/absence of anti–HIV-1 antisera. | ↓ CFU-GM & ↓ BFU-E only in presence of antisera. | Not evaluated. | HIV-1 in pooled colonies from 1/4 patients (RT activity in culture supernatants). | No convincing evidence of progenitor cell infection. More differentiated cells in culture may be virus source. Anti-gp120 antibodies may be suppressive elements in patient sera. |
| Lunardi-Iskandar et al11 | BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | Not evaluated. | Not evaluated. | Depletion of adherent cells or T cells or addition of cytokines (GM-CSF, IL-3, Epo) did not restore colony growth). |
| Molina et al27 (see Table 1) | BM cells from HIV-1+ patients seeded into colony assays. | Colony growth normal. | Not evaluated. | No HIV-1 DNA detected (gag PCR). | No evidence of progenitor cell infection. Propose cytopenias due to alteration in BM microenvironment. |
| Von Laer et al183 | Culture of purified CD34+ BM cells from HIV-1+ patients. | Not evaluated. | HIV-1 DNA detected in 1/14 samples (gag PCR). | Not evaluated. | No convincing evidence of progenitor cell infection. Single positive attributed to CD4+ T-cell contamination. |
| Ganser et al184 | BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-GEM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | No HIV-1 detected (immunohistochemistry and in situ hybridization). | No evidence of progenitor cell infection. |
| Davis et al28 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-E | HIV-1 DNA detected in 1/11 samples (gag/env PCR). | No HIV-1 DNA detected (gag/env PCR). | No convincing evidence of progenitor cell infection. Single positive attributed to CD4+ T-cell or MΘ contamination. |
| Kojouharoff et al175 (see Table 2) | BM cells from HIV-1+ patients seeded into colony assays. | Colony growth normal. | Not evaluated. | HIV-1 mRNA detected in CFU-GEM & CFU-GM in 2/6 patients (in situ hybridization) | No convincing evidence of progenitor cell infection. HIV-1+ cells may reflect infection of a more differentiated phenotype. |
| Zauli et al25 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-E ↓ CFU-Mk | No HIV-1 DNA (gag PCR) or protein (p24 ELISA) detected. | Not evaluated. | No evidence of progenitor cell infection. HIV-1 detected in unfractionated bone marrow samples. A role for HIV-1 in the BM microenvironment proposed. |
| Zauli et al185 | Purified CD34+ BM cells from HIV-1+patients seeded into colony assays. | ↓ CFU-GM ↓ CFU-Mk | HIV-1 DNA detected in 2/17 samples (gag/env PCR). No p24 in culture supernatants. | Not evaluated. | No convincing evidence of progenitor cell infection. Two positives attributed to CD4+ T-cell or MΘ contamination. 9 CFU-Mk in all samples implies an indirect mechanism. |
| Stanley et al150 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | HIV-1 DNA (gag/env PCR) & virus (co-culture) detected in 17/52 & 8/29 Zairian and 3/22 & 1/2 American samples. | Not evaluated. | HIV-1 detected only in subset of patients with advanced disease. 9 CFU-GM & 9 BFU-E in all samples implies an indirect mechanism. CD34+ accessory cells are potential source of HIV-1. |
| Louache et al186 | BM cells from 27 HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E ↓ CFU-Mk | Not evaluated. | No HIV-1 DNA detected (gag PCR). | No evidence of progenitor cell infection. Anti-sense nef or tat increased clonal growth. |
| Kaczmarski et al187 | BM cells from HIV-1+ patients studied in LTBMC and colony assays. | Normal CFU-GEMM and CFU-GM. | Not evaluated. | HIV-1 DNA detected in pooled CFU-GEMM, CFU-GM & CFU-LTC (gag/env/tat PCR). | No convincing evidence of progenitor cell infection. No T-cell depletion so infection of differentiating cells could not be ruled out. |
| De Luca et al29 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | No HIV-1 DNA detected (gag PCR). | Not evaluated. | No evidence of progenitor cell infection. |
| Hillyer et al7 | Purified CD34+ cells from SIV-infected macaques seeded into colony assays. | ↓ CFU-GM ↓ BFU-E | No SIV DNA detected (gag PCR). | SIV DNA detected in occasional pooled CFU-GM colonies. | No convincing evidence of progenitor cell infection. Rare positive signal attributed to CD4+ T-cell or MΘ contamination. |
| Neal et al34 | Purified CD34+ BM cells from HIV-1+ patients studied in LTBMC and colony assays. | Normal CFU-E, BFU-E, CFU-GM & cobblestone formation in LTBMC. | HIV-1 DNA detected in 2/10 patients (gag/pol PCR). | All pooled CFU-GM were HIV-1 DNA negative (gag/pol PCR). 1/5 pooled CFU-E/BFU-E were weakly HIV-1+ (<2 copies/75,000 cells). | No convincing evidence of progenitor cell infection. Low proviral DNA copy number in pooled colonies (2-5 copies/250,000 cells) suggests (CD4+ T-cell or MΘ contamination. |
| Dallalio et al188 | Purified CD34+ BM cells from 5 HIV-1+ patients seeded into CFU-E assays | Normal CFU-E. | Not evaluated. | Not evaluated. | CFU-E were not more sensitive to cytokine-mediated inhibition of colony formation. |
| Slobod et al31 | Mobilization of CD34+ BM cells from HIV-1+ patients. Nested PCR for evidence of HIV-1 infection. | Not evaluated. | HIV-1 DNA in 2/7 patients but in only 1/3 replicate samples (nested env PCR detecting 1 DNA copy/25,000 cells). | Not evaluated | No convincing evidence of progenitor cell infection. CD34+ cells at 92-99% purity so variable positives attributed to CD4+T-cell contamination. |
| Marandin et al189 | Primitive BM cells from HIV-1+ patients evaluated by flow cytometry. Fractionated CD34+ cells studied in LTBMC and colony assays. | ↓ CFU-GM ↓ BFU-E ↓ LTC-IC | No HIV-1 DNA detected (gag PCR). Included separate analysis of CD34+/CD4+, CD34+/CD38+ & CD34+/CD38− populations. | No HIV-1 DNA detected (gag PCR). | No significant change in percentage of CD34+ cells in HIV-1+ patients but proportions of CD34+/CD38− & CD34+/Thy 1+ cells decreased. Suggests loss of more primitive phenotype but not via direct infection. |
| Kearns et al151 | Purified CD34+ BM cells from HIV-1+ patients seeded into colony assays. | ↓ CFU-GM | HIV-1 DNA detected in rare samples. Semi-quantitative PCR estimates 1/100,000 cells infected. | Not evaluated. | No evidence of significant progenitor cell infection. Propose dysregulated hematopoiesis due to alterations in the BM microenvironment. |
| Bahner et al52 | Ex vivo infection of human marrow stromal cells with HIV-1 and stomal cells genetically modified to resist HIV-1 infection. Stroma overlayered with bone marrow cells. | ↓ CFU-GM (obtained after 3 wk on stroma) | Not evaluated. | Not evaluated. | Stroma is infectable. Reduced capacity of HIV-1-infected stroma to support hematopoietic progenitor cell growth. |
Abbreviations: NATD, nonadherent T-cell depleted; MΘ, macrophage.