The in 1980, belongs to the Deltaretrovirus genus of

The human T-lymphotropic
virus type 1 (HTLV-1), firstly identified in 1980, belongs to the Deltaretrovirus genus
of the Retroviridae family 1. The second type, HTLV-2, was isolated shortly afterwards 2, followed by HTLV-3,
and HTLV-4, 3-4. All types of HTLV (1, 2, 3
and 4) can infect humans, but only HTLV-1 has been persuasively associated with the development of human diseases
5.

Based on previous studies,
HTLV-1 is endemic in certain regions of
the world, including the South of Japan, the Caribbean islands, Africa, South
America and parts of Iran 6. There are 15-20 million infected people in
the world, but the majority of them (more
than 95%) remain asymptomatic (healthy carriers) 7. HTLV-1 is the etiological agent of aggressive
leukemia, called adult T-cell leukemia-lymphoma
(ATL) 5. ATL is divided into four clinical subtypes, namely acute, lymphoma-­type,
chronic, and smoldering 8. HTLV-1 infection is also associated with several other disorders including HTLV-1
associated myelopathy/tropical spastic paraparesis (HAM/TSP), uveitis, arthritis,
alveolitis/bronchiectasis, dermatitis, and
lymphadenitis, but there are few data on
prevalence 9-13.

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Both ATL and HAM/TSP have a
low incidence among HTLV-1 individuals and only
2-6% of HTLV-1 carries

develop ATL, and a further 2–3% develop HAM/TSP, with a
long period of clinical latency after viral infection 5, 14. This manuscript is a review of
the recent developments regarding HTLV-1 enzymes, envelope glycoproteins, and
accessory proteins Tax and HBZ as therapeutic targets for the treatment of HTLV-1
infection.

The HTLV-1 genome has
structural genes, gag, pol, pro, env, as well as a pX region flanked by 5′ and 3′ long terminal repeat (LTR)
sequences at both ends (Fig. 1). The 5´LTR serves as the main
promoter for viral transcription. In ATL patients, the 5′ LTR frequently
undergoes deletion and methylation, while the 3′ LTR always remains intact 15-16. In HTLV-1, the pro
and pol genes encode the proteins that are synthesized by a
frameshifting mechanism from genome-sized RNA templates to produce Gag-Pro and
Gag-Pro-Pol precursors. The Gag precursors encode
the virion structural proteins (matrix (MA), capsid (CA), nucleocapsid (NC)),
while proteolytic processing of Gag-Pro precursors during maturation yields transframe protein (TF), protease (PR) and two
smaller fragments (p1 and p2). The Gag-Pro-Pol precursors are processed into MA, CA, TF, PR, p1, reverse
transcriptase (RT) and integrase (IN). The HTLV-1 genome also contains a pX region located between the env gene and the 3´ LTR. The pX region
contains sequences for viral regulatory and accessory proteins, Tax, Rex, p12,
p13, p30 and p21 and HTLV-1 bZIP factor
(HBZ) which are involved in viral infectivity and pathogenicity 17.