Vicenzi E, Panina-Bordignon P, Poli G; International Conference on AIDS.

Int Conf AIDS. 2000 Jul 9-14; 13: abstract no. TuOrA344.

E. Vicenzi, San Raffaele Scientific Institute, P2-P3 Laboratories, DIBIT, Via Olgettina n. 58, 20132, Milano, Italy, Tel.: +39 2 2643 4908, Fax: +39 2 2643 4908, E-mail: poli.guido@hsr.it

Background: CD4+ T cells may undergo functional polarization into Th1 or Th2 cells, secreting either IFN-g or IL-4, respectively. Early studies indicated that HIV replication was impaired in Th1, but not in Th2 or unpolarized T cell clones. Methods: Infection of Th1 or Th2 polarized or unpolarized (Th0) T cell clones or cord blood lines by different laboratory-adapted and primary HIV strains characterized by differential usage of chemokine receptors was monitored by RT activity, quantitative HIV DNA PCR and by additional assays. Results: We have recently demonstrated that both primary and laboratory-adapted CCR5-monotropic HIV strains (R5 viruses) replicated with comparable efficiency in Th1, Th0, and Th2 T cell clones and cord blood-derived T cell lines (CB lines). In sharp contrast, CXCR4-dependent viruses (X4 strains) did not replicate efficiently in these cells despite expression of functional CXCR4 on their cell surface unless cells were mitogenically activated by anti-CD3 mAbs (E. Vicenzi et al., J Virol 73:7515,1999). We have now tested primary dualtropic (R5/X4, R3/X4) HIV isolates for their capacity to replicate in Th-1, Th0, Th-2 CB lines and clones. These isolates replicated in Th2 and Th0 cells, but were strongly restricted in Th1 cells. Kinetic analysis of proviral DNA accumulation indicated that dualtropic HIVs readily infected Th-1 cells, but, unlike R5 viruses, failed to spread efficiently thereafter. Conclusions: These results suggest that: A. R5 viruses have a selective replicative advantage over X4 strains in that they can replicate in sub-optimally activated CD4+ T cells, and, B., polarization along the Th2 pathway may favor the emergence of dualtropic HIVs, typically observed in more advanced stages of clade B HIV disease. We are currently investigating the role of endogenous polarizing cytokines in determining the observed patterns of virus replication.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Antigens, CD4
• CD4-Positive T-Lymphocytes
• Cell Line
• Cytokines
• HIV
• HIV Envelope Protein gp120
• HIV Infections
• HIV Long-Term Survivors
• HIV Seropositivity
• Interferon Type II
• Interleukin-4
• Receptors, CCR5
• Receptors, CXCR4
• Th1 Cells
• Th2 Cells
• Virus Replication
• immunology
• virology

Other ID:

• GWAIDS0001302

UI: 102238793

From Meeting Abstracts