Human T-cell Lymphotropic Viruses (HTLV)
In 1980, it became possible to propagate human T lymphocytes with the help of IL-2. Long term cultivation of lymphocytes from patients with T cell leukaemias yielded retrovirus with C-type morphology. HTLV-I and II share most properties such as density, morphology, a 70S RNA, reverse transcriptase and structural proteins with all other replication-competent C-type retrovirus. The major HTLV core protein p24 was shown to be serologically distinct from the core proteins of all previously described viruses. HTLV-I and HTLV-II are often dubbed the "forgotten human retroviruses" in the wake of the massive and unprecedented attention and resources dedicated to HIV. It should not be forgotten though that the discovery of HTLC-I paved the way for the discovery of HIV.
Belong to the oncornavirus subfamily of retroviruses
ssRNA enveloped virus
Two copies of the RNA genome with 3 major genes:
gag (structural proteins, pol (reverse transcripatse), and env (envelope glycoproteins)
Both HTLV-I and HTLV-II are tropic for OKT4+ T-helper lymphocytes but other cells can be infected.
In contrast to HIV, the cellular receptor is not known.
Both HTLV-I and HTLV-II can transform suitable target cells in vitro.
Despite the ability to transform, both viruses do not possess a specific oncogene
Seroepidemiological studies reveal that HTLV-I infection
occurs in clusters in certain geographic locations around the
world. It is endemic in Southern Japan (15-30%), Caribbean
(3-6%), Papua New Guinea and some parts of Africa. HTLV-I appears
to be transmitted sexually and through blood. Vertical
transmission is thought to play an important role in the
maintenance of virus in areas of high endemicity. Transmission
through breast milk is implicated as a major route for the
maintenance of infection in high prevalence areas. Seroprevalence
of HTLV-I increases with age and is twice as high in females than
males. In Southern Japan, HTLV-I seroprevalence in persons over
80 years was 50% in females and 30% in males. This gender
difference usually emerges after 30 years and probably reflects
more efficient transmission from males to females during sexually
active years. HTLV- II infection is particularly common in IV
drug abusers, and has been found in clusters among certain South
C. Disease Associations
HTLV-I is associated with at least 2 kinds of disease manifestation; adult T-cell leukaemia and tropical spastic paraparesis.
There is a possibility that some of the agents currently in
use against HIV, especially the nucleoside analogue inhibitors,
may work against HTLV-1. However, since ATL and TSP present years
following infection, there appears little justification in using
antiviral therapy in healthy carriers. A combination of
interferon-alpha and zidovudine had been reported to be effective
in treating ATL patients. A combination of zidovudine, danazol,
and Vitamin C in providing temporary relief for TSP patients.
Screening of blood donations for HTLV-I is now routinely carried out in high prevalence areas such as Japan. However, there is a trend towards screening in low prevalence areas as well e.g. USA and France. In other low prevalence areas, screening is only carried out on donors who originate from high prevalence areas e.g. Japan and the Carribean. In Japan, antenatal screening for HTLV-1 antibody is carried out for pregnant wowen. Those who are positive are advised not to breastfeed their infants. Research is being carried out on the development of a vaccine against HTLV-I.