Reciprocal functional pseudotyping of HIV-1 and HTLV-1 viral genomes by the heterologous counterpart envelope proteins

Abstract

HIV-1 and HTLV-1 can infect CD4+ T cells and can co-infect the same individual. In principle, it is possible that both viruses can infect the same CD4+ T cells in dually infected persons. Currently, how efficiently HTLV-1 and HIV-1 co-infects the same cell and the full extent of their biological interactions are not well-understood. Here, we report evidence confirming that both viruses can infect the same cells and that HTLV-1 envelope (Env) can pseudotype HIV-1 viral particles and HIV-1 envelope (Env) can pseudotype HTLV-1 virions to mediate subsequent infections of substrate cells. We also show that the construction of a chimeric HTLV-1 molecular clone carrying the HIV-1 Env in place of its HTLV-1 counterpart results in a replication competent moiety. These findings raise new implications of viral complementation and assortment between HIV-1 and HTLV-1 in dually infected persons.

Pseudotyping of HIV-1 with Human T-Lymphotropic Virus 1 (HTLV-1) Envelope Glycoprotein during HIV-1–HTLV-1 Coinfection Facilitates Direct HIV-1 Infection of Female Genital Epithelial Cells: Implications for Sexual Transmission of HIV-1

“…This observation held true when these two retroviruses replicated in primary CD4 + T lymphocytes, as well as CD4 + T cell lines. Although published studies show that HIV-1–HTLV-1 coinfection of T cell lines can generate HIV-1 virions with expanded cell tropism that can infect non-CD4-expressing cell such as B cells and CD8 + T cells ( 35 – 38 ), these studies, which date back 30 years, were largely discontinued. Furthermore, how these observations related to HIV-1 transmission and pathogenesis was not explored.…”

“…Because the tropisms of HTLV-1 and HIV-1 overlap (i.e., CD4 + T cells) and they use distinct receptors, these viruses can coinfect the same cells and coinfection could facilitate acquisition of the HTLV-1 Env protein by HIV-1, rendering the latter virus capable of infecting non-CD4-expressing cells. Evidence that coinfection with HTLV-1 in T cell lines can broaden HIV-1 cellular tropism and enable it to infect non-CD4-expressing cells such as B cells and CD8 + T cells has been reported ( 34 – 38 ). However, whether pseudotyping of HIV-1 during coinfection with HTLV-1 could occur in primary T cells and in vivo has not been explored.…”

Leukemia and Retroviral Disease

“…Both HIV and HTLV-1 share CD4 + T cells as their cell target, which was further demonstrated by complementation viral envelopes for each other [84]. In addition to the CD4 + T-cell compartment, a number of other human cellular compartments are infected by HIV-1, including cells of the monocyte-macrophage lineage, some subsets of dendritic cells, microglial cells and astrocytes within the brain, hematopoietic progenitor cells, and endothelial cells lining the blood-brain barrier [85,86].…”

HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment

“…In vitro co-infection of a given CD4+ T-cell by both HTLV-1 and HIV-1 has been reported [ 143 ]. In addition, co-infection of HTLV-1-infected cells by HIV-1 is also possible [ 144 ], suggesting the potential presence of both viruses in the same CD4+ T-cells in co-infected individuals.…”