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• Macchi, B
• Balestrieri, E
• Ascolani, A
• Hilburn, S
• Martin, F
• Mastino, A
• Taylor, G
• [+] on Google Scholar
• Macchi, B
• Balestrieri, E
• Ascolani, A
• Hilburn, S
• Martin, F
• Mastino, A
• Taylor, G
• [+] on PubMed
• Macchi, B
• Balestrieri, E
• Ascolani, A
• Hilburn, S
• Martin, F
• Mastino, A
• Taylor, G

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Viruses 2011, 3(5), 469-483; doi:10.3390/v3050469

Article

Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors

Beatrice Macchi ^1,5 , Emanuela Balestrieri ¹ , Arianna Ascolani ¹ , Silva Hilburn ² , Fabiola Martin ³ , Antonio Mastino ^4,6  and Graham P Taylor ^2,3,*

¹ Department of Neuroscience, University of Rome “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy ² Department of Communicable Diseases, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK ³ National Centre for Human Retrovirology, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, Praed St, London W2 1NY, UK ⁴ Department of Life Sciences, Section of Microbiological, Genetic and Molecular Sciences, University of Messina, Via F. Stagno d’Alcontres 31, 98166, Messina, Italy ⁵ IRCCS, Santa Lucia, Via Ardeatina 306, 00179, Rome, Italy ⁶ 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

(This article belongs to the Special Issue Recent Developments in HTLV Research)

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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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