Journal of Medical Virology Evaluation of HTLV-1 HBZ and Proviral Load, Together With Host IFN l3, in Pathogenesis of HAM/TSP Sayed-Hamidreza Mozhgani, 1 Najmeh Jaberi, 1 Seyed Abdolrahim Rezaee, 2 Reza Bustani, 3 Seyed Mohammad Jazayeri, 1 Mohammad Mehdi Akbarin, 2 Saeideh Milani, 4 Hanieh Tarokhian, 2,5 and Mehdi Norouzi 1 * 1 Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2 Inflammation and Inflammatory Disease Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3 Department of Neurology and HTLV-1 Foundation, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 4 Department of Biotechnology, School of Medicine, Shahid-Beheshti University of Medical Sciences, Tehran, Iran 5 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran Human T-cell lymphotropic virus 1 (HTLV-1) is associated with two progressive diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leuke- mia/lymphoma (ATLL). Although HTLV-1 provi- ral load (PVL) has been introduced as a risk factor for these diseases’ progression, it is not sufficient on its own to yield an accurate estimation of the outcome of the infection. In the present study, PVL and HTLV-1 basic leucine zipper factor (HBZ) expression level as viral factors, and IFN l3 as a host factor, were evaluated in HAM/TSP patients and HTLV-1 asymptomatic carriers (ACs). During 2014–2015, 12 HAM/TSP patients and 18 ACs who had been referred to the HTLV-1 Clinic, Ghaem Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and the DNA and mRNA were extracted for quantification of HBZ, IFN l3 expression, and PVL using real-time PCR (Taq- Man method). Although the PVL was higher in the HAM/TSP group, with a 94% confidence interval, there were no considerable differences in terms of HBZ mRNA and PVL between ACs and HAM patients. IFN l3 expression in the HAM/TSP group was significantly higher than in the ACs (P ¼ 0.02). To the best of our knowledge, no study has evaluated the expression level of IFN l3 in HTLV-1 positive patients.The immune response against HTLV-1 viral antigens and virulent factors will therefore further refine our knowledge of interactions between the virus and host in the pathogenesis of HTLV-1-related disorders. The virus PVL and the host IFN l3 can be used as pathogenic factors of HTLV-1 in- fected patients at risk of HAM/TSP manifesta- tion. J. Med. Virol. # 2016 Wiley Periodicals, Inc. KEY WORDS: human T-lymphotropic virus type 1; human T-lymphotropic virus type 1-associated myelo- pathy/tropical spastic parapar- esis; proviral load; IFN l3; HBZ INTRODUCTION Human T-lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus that is estimated to infect 10–20 million people worldwide [Gessain and Cassar, 2012]. Groups at high risk of endemicity from HTLV-1 have been identified in the southern islands of Japan, the Caribbean, sub-Saharan Africa, and parts of South America [Ramezani et al., 2012; Martin et al., 2014]. The main endemic areas in Iran are the northeastern provinces, with a prevalence of 5–25% [Tabei, 2011]. In spite of HIV-positive patients, most (>90%) HTLV-1-positive individuals remain healthy, as do asymptomatic carriers (ACs) [Hanon et al., 2001]. A small proportion of HTLV-1-infected individuals dev- elop a type of neoplastic disease called adult T-cell leukemia/lymphoma (ATLL) and the inflammatory  Correspondence to: Mehdi Norouzi, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. E-mail: mnorouzi@tums.ac.ir Accepted 25 October 2016 DOI 10.1002/jmv.24721 Published online in Wiley Online Library (wileyonlinelibrary.com).  C 2016 WILEY PERIODICALS, INC.