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 language | English (US) |
|---|---|
| Pages (from-to) | 1661-1668 |
| Number of pages | 8 |
| Journal | AIDS Research and Human Retroviruses |
| Volume | 16 |
| Issue number | 16 |
| DOIs | |
| State | Published - Nov 1 2000 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - In vitro cellular tropism of human T cell leukemia virus type 2
AU - Wang, T. G.
AU - Ye, J.
AU - Lairmore, Michael Dale
AU - Green, P. L.
PY - 2000/11/1
Y1 - 2000/11/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0034331219&partnerID=8YFLogxK
U2 - 10.1089/08892220050193119
DO - 10.1089/08892220050193119
M3 - Article
C2 - 11080807
AN - SCOPUS:0034331219
VL - 16
SP - 1661
EP - 1668
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 16
ER -