Infection of hematopoietic progenitor cells by HIV-1 subtype C, and its association with anemia in southern Africa

Abstract

Reports from southern Africa, an area in which human immunodeficiency virus type 1 (HIV-1) infection is caused almost exclusively by subtype C (HIV-1C), have shown increased rates of anemia in HIV-infected populations compared with similar acquired immunodeficiency syndrome (AIDS) patients in the United States, an area predominantly infected with subtype B (HIV-1B). Recent findings by our group demonstrated a direct association between HIV-1 infection and hematopoietic progenitor cell health in Botswana. Therefore, using a single-colony infection assay and quantitative proviral analysis, we examined whether HIV-1C could infect hematopoietic progenitor cells (HPCs) and whether this phenotype was associated with the higher rates of anemia found in southern Africa. The results show that a significant number of HIV-1C, but not HIV-1B, isolates can infect HPCs in vitro (P < .05). In addition, a portion of HIV-1C-positive Africans had infected progenitor cell populations in vivo, which was associated with higher rates of anemia in these patients (P < .05). This represents a difference in cell tropism between 2 geographically separate and distinct HIV-1 subtypes. The association of this hematotropic phenotype with higher rates of anemia should be considered when examining anti-HIV drug treatment regimens in HIV-1C-predominant areas, such as southern Africa.

Figure 1

Verification of HIV-1 infection of HPC-CFUs by Alu-LTR integration. (A) Infected colonies and blank wells were tested for integration using nested PCR. The resulting DNA product was approximately 150 bp in length. 8E5 cellular DNA (lanes 1-4: 50 000, 5000, 500, and 50 copies, respectively), a blank MJ4 well as the negative control (lane 5), MJ4-infected BFU-E colonies (lanes 6-8), MJ4-infected CFU-GM colonies (lanes 9-13), the MHX-infected CFU-GM colony (lane 14), BW-2036–infected BFU-E colonies (lanes 15, 16), BW-2036–infected CFU-GM colonies (lanes 17, 18), and H₂O (lane 19) are shown. (B) Representative fluorescent curves of SYBR Green integration assay. Standards are indicated as copy number of 8E5 cellular DNA; positive colony types and negative blank wells from MJ4 and patient 13 are also shown with colors indicated in parentheses.

Figure 2

Efficiency of single-colony infections using primary HIV-1 isolates. Total colonies infected are shown as percentage of colonies tested. All colonies were compared with HXB2RU3CI for significance. Cloned virus isolates are shown (▨). The percentage of HIV-1C isolates that infect progenitor cells differs significantly from the percentage of HIV-1B as determined by Fisher exact test, P < .05.