Transcriptional effects of superinfection in HIV chronically infected T cells: Studies in dually infected clones

Jerome H. Kim, Robert J. McLinden, Joseph D. Mosca, Donald S. Burke, R. Neal Boswell, Deborah L. Birx, Robert R. Redfield

Research output: Contribution to journalArticlepeer-review

Abstract

We had previously shown that chronically infected ACH-2 cells (HIV(LAI) could be superinfected with HIV(RF), that the frequency of superinfection increased with time, and that the transcription of the superinfecting virus exceeded that of the host HIV(LAI) provirus. In contrast, ACH-2 cells superinfected with a nef-substituted neomycin-resistant (proNEO) provirus were not detectable by DNA polymerase chain reaction (PCR) until geneticin (G418) was added, suggesting that the ability to propagate progressively in culture may be HIV strain specific. Clonal populations of ACH-2 superinfected with proNEO did not demonstrate preferential transcription of the superinfecting virus. However, clones of ACH-2 superinfected with HIVRf (ACH2/RF) showed a preponderance of HIV(RF), transcripts similar to that seen in bulk populations. Induction of the superinfecting virus by phorbol ester (PMA) occurred more rapidly than the host provirus and did not equalize transcriptional activity. PCR-derived long terminal repeat (LTR) fragments and Tat cDNAs from A3.01 cells acutely infected with HIVRF or from ACH-2 cells were sequenced and tested for transactivation. The HIV(LAI) LTR was two to three times more Tat-responsive than the HIV(RF) LTR. Tat(RF), was two to three times more transcriptionally active on either LTR than Tat(LAI). Demethylation with 5-azacytidine did not significantly affect HIV expression from the HIV(LAI) host provirus of superinfected ACH2/RF cell clones. These data suggest that the mechanism of preferential transcription in HIV(RF) superinfected ACH2/RF may be attributed to the Tat/TAR axis and the effect of the specific locus of host proviral integration.

Original languageEnglish (US)
Pages (from-to)329-342
Number of pages14
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume12
Issue number4
DOIs
StatePublished - 1996

Keywords

  • Dual infection
  • HIV-1 superinfection
  • Transcription HIV-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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