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Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors
Department of Neuroscience, University of Rome “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy
Department of Communicable Diseases, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK
National Centre for Human Retrovirology, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, Praed St, London W2 1NY, UK
Department of Life Sciences, Section of Microbiological, Genetic and Molecular Sciences, University of Messina, Via F. Stagno d’Alcontres 31, 98166, Messina, Italy
IRCCS, Santa Lucia, Via Ardeatina 306, 00179, Rome, Italy
IRCCS Centro Neurolesi “Bonino- Pulejo”, Via Provinciale Palermo, 98124 Messina, Italy
* Author to whom correspondence should be addressed.
Received: 25 February 2011; in revised form: 6 April 2011 / Accepted: 21 April 2011 / Published: 5 May 2011
Abstract: Since human T-lymphotropic virus type 1 (HTLV-1)-associated diseases are associated with a high HTLV-1 load, reducing this load may treat or prevent disease. However, despite in vitro evidence that certain nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) are active against HTLV-1, in vivo results have been disappointing. We therefore assayed the sensitivity of HTLV-1 primary isolates to a panel of RT inhibitors. HTLV-1 primary isolates were obtained, pre- and post- NRTI treatment, from patients with HTLV-1-associated myelopathy. Sensitivity to azidothymidine (AZT), lamivudine (3TC), tenofovir (TDF) and three phosphonated carbocyclic 2’-oxa-3’aza nucleosides (PCOANs) was assessed in a RT inhibitor assay. With the exception of 3TC, HTLV RT from primary isolates was less sensitive to all tested inhibitors than HTLV-1 RT from MT-2 cells. HTLV-1 RT from primary isolates and from chronically infected, transformed MT-2 cells was insensitive to 3TC. Sensitivity of primary isolates to RT inhibitors was not reduced following up to 12 months of patient treatment with AZT plus 3TC. The sensitivity of HTLV-1 primary isolates to NRTIs differs from that of cell lines and may vary among patients. Failure of NRTIs to reduce HTLV-1 viral load in vivo was not due to the development of phenotypic NRTI resistance. AZT and the three PCOANs assayed all consistently inhibited primary isolate HTLV-1 RT.
Keywords: Human T-cell Lymphotropic Virus type 1; primary isolates; reverse transcriptase; drug sensitivity; azidothymidine; lamivudine; tenofovir; phosphonated carbocyclic 2’-oxa-3’aza nucleosides
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Macchi, B.; Balestrieri, E.; Ascolani, A.; Hilburn, S.; Martin, F.; Mastino, A.; Taylor, G.P. Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors. Viruses 2011, 3, 469-483.
Macchi B, Balestrieri E, Ascolani A, Hilburn S, Martin F, Mastino A, Taylor GP. Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors. Viruses. 2011; 3(5):469-483.
Macchi, Beatrice; Balestrieri, Emanuela; Ascolani, Arianna; Hilburn, Silva; Martin, Fabiola; Mastino, Antonio; Taylor, Graham P. 2011. "Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors." Viruses 3, no. 5: 469-483.