In vitro cellular tropism of human T cell leukemia virus type 2

T. G. Wang, J. Ye, Michael Dale Lairmore, P. L. Green

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Human T cell leukemia virus type 1 (HTLV-1) and 2 (HTLV-2) are distinct oncogenic retroviruses that infect several cell types, but display their biologic/pathogenic activity only in T lymphocytes. HTLV-1 is associated with adult T cell leukemia, a malignancy of mature CD4+ T cells, and a chronic neurological disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-2 is less pathogenic and has been associated with a few cases of a variant of hairy cell leukemia and neurological disease. Previous studies have indicated that in viva HTLV-1 has a preferential tropism for CD4+ T cells, whereas HTLV-2 in vivo tropism is less clear, but appears to favor CD8+ T cells. The molecular mechanism that determines the cellular tropism of HTLV-1 and HTLV-2 has not been precisely determined. However, one study by our group has provided evidence that HTLV-1-enhanced viral transcription in CD4+ T cells may be responsible for its tropism. In an effort to understand HTLV-2 tropism we tested the ability of HTLV-2 to infect, replicate in, and transform purified CD4+ or CD8+ T cells in cell culture. After cocultures of purified primary human CD4+ and CD8+ T cells with an HTLV-2-producer cell line we measured viral transcription by reverse transcription PCR analysis, virus production by p19(gag) ELISA, proviral integration by DNA slot-blot analysis, surface phenotype by FACS analysis, and cellular transformation. We also measured HTLV-2 long terminal repeat-directed transcription in the presence and absence of Tax in purified CD4+ and CD8+ T cells, using transient transfection assays. Our data indicate that CD4+ and CD8+ cells are equally susceptible to HTLV-2 infection. We observed no significant difference in viral transcription based on mRNA and virus production in CD4+ and CD8+ T cell cocultures. Although LTR transcription was enhanced 12- to 16-fold in the presence of Tax, there was no significant difference in CD4+ or CD8+ T cells. Interestingly, we show that HTLV-2 preferentially transforms CD8+ T cells in culture. Together, our data indicate that, unlike HTLV-1, HTLV-2 cell tropism is not due to inhibition of viral infection and inefficient gene expression in CD4+ versus CD8+ T cells, and likely involves unique interactions with viral and CD8+ T cell-specific proteins.

Original languageEnglish (US)
Pages (from-to)1661-1668
Number of pages8
JournalAIDS Research and Human Retroviruses
Volume16
Issue number16
DOIs
StatePublished - Nov 1 2000
Externally publishedYes

Fingerprint

Deltaretrovirus
Tropism
Human T-lymphotropic virus 2
Human T-lymphotropic virus 1
T-Lymphocytes
Coculture Techniques
In Vitro Techniques
Cell Culture Techniques
Tropical Spastic Paraparesis
Viruses
Hairy Cell Leukemia
Adult T Cell Leukemia Lymphoma
Terminal Repeat Sequences
Spinal Cord Diseases
Virus Diseases
Retroviridae
Nervous System Diseases
Biological Products
Reverse Transcription
Transfection

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

In vitro cellular tropism of human T cell leukemia virus type 2. / Wang, T. G.; Ye, J.; Lairmore, Michael Dale; Green, P. L.

In: AIDS Research and Human Retroviruses, Vol. 16, No. 16, 01.11.2000, p. 1661-1668.

Research output: Contribution to journalArticle

Wang, T. G. ; Ye, J. ; Lairmore, Michael Dale ; Green, P. L. / In vitro cellular tropism of human T cell leukemia virus type 2. In: AIDS Research and Human Retroviruses. 2000 ; Vol. 16, No. 16. pp. 1661-1668.
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