生物谷引大公报报道：香港大学医学院成功破解由病毒感染引致人类T细胞白血病病毒1型（HTLV-1），的机制，有助开发新一代抗癌药物。这种白血病在香港比较少见，过去五、六年约有六至七宗死亡个案，其中半数是在日本经性接触感染病毒。
负责研究的医学院生物化学系助理教授金冬雁昨在记者会说，他们的基础研究，对研制抗癌药物有启示作用，尤其是对血癌、肝癌、鼻胭癌与子宫颈癌等透过病毒传染的癌症最为有用，但估计真正成功研制药物最少需数十年。
这种白血病的病毒感染途径与艾滋病相同，在港人中很少见，少于百分之零点一人口携有这种人类T细胞白血病病毒1型（HTLV-1），但这种病毒局部在一些地方颇活跃，如日本南部、福建、台湾、非洲和南美等地。
在日本南部 ，五十多岁以上的男性人口中，三至四成带有此病毒，同龄组别女性人口中更多。香港这个疾病比较少见，过去五、六年约有六至七宗死亡个案，据发病者感染途径监测，其中两三人在日本时经性接触感染病毒。疾病死亡率是百分之一百，而且来势汹汹，病发后病人只有几个月寿命。全世界有二千多万人感染HTLV-1病毒，须经过漫长的二十至五十年潜伏期后，才在约百分之五的感染者中发病。
病毒感染是导致癌症的其中一个主要原因。据估计全球大约百分之十五的癌症与病毒有关。香港病发率较高的肝癌、鼻咽癌症及子宫颈癌，便是病人感染乙型肝炎病毒、EB毒和人类乳瘤病毒引致。他们今次研究的重要性，揭示病毒致癌的一种新机理，可能亦对研制新一代的致癌药物，如治疗肝癌、鼻咽癌及子宫颈癌药物，有启示的作用。
HTLV-1型病毒的发现、属性特点，致病及预防简介
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.
A. Properties
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
B. Epidemiology
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 American Indians.
C. Disease Associations
HTLV-I is associated with at least 2 kinds of disease manifestation; adult T-cell leukaemia and tropical spastic paraparesis.
Adult T-cell leukaemia - the evidence implicating HTLV-I as the aetiological agent of ATL includes the association of ATL with HTLV-I antibodies, the isolation of the virus, the finding of monoclonal integrated proviral sequences in leukaemic cells of patients with ATL, and epidemiological data. ATL, in the majority of cases, is a rapidly progressive fatal disease and affects 1 in 500 of persons infected by HTLV-I. It is characterized by diffuse lymph node infiltration, hypercalcaemia, leukaemia, skin infiltrates, and a positive HTLV-I antibody test. An incubation period of 15 to 20 years have been suggested for the development of ATL.
Tropical Spastic Paraparesis - the association of HTLV-I with TSP was discovered in 1985 while screening blood donors for HTLV-I antibodies in Martinique, West Indies. More than 75% of patients with TSP were found to have antibodies against HTLV-I and the association is further supported by the isolation of HTLV-I from the blood and CSF of patients with TSP. A chronic neurological disorder identical with TSP was found subsequently in other regions endemic for HTLV-I such as Africa and Japan, where TSP was named HTLV-I associated myelopathy. Clinically, TSP resembles multiple sclerosis, but lacks the intracranial nerve signs and remissions characteristic of MS. Initial symptoms are bilateral weakness and stiffness of the lower extremities. The course is slowly progressive, usually with bladder involvement, but shows considerable variations.
Other Associations - HTLV-I infection has been associated with a large variety of clinical syndromes, of which there is strong evidence in the case of HTLV-I associated infective dematitis and HTLV-I associated uvetis. It is likely that the spectrum of disease associations with increase with time.
D. Laboratory_Diagnosis
Serology - Laboratory diagnosis rests mainly on the detection of antibodies against using screening EIAs. A passive particle agglutination assay (Serodia) is also available and is widely used in Japan for the screening of blood donations. Current EIAs cannot distinguish between HTLV-I and HTLV-II. However, a commercial Western blot using recombinant HTLV antigens are available which can distinguish between HTLV-I and HTLV-II. There appears to be some correlation between the titre of anti-HTLV-I antibody and the likelihood of developing ATL and TSP in HTVL-I carriers.
Detection of proviral DNA - PCR can also be used to detect HTLV from peripheral blood mononuclear cells and can distinguish between HTLV-1 and HTLV-II. There is also interest in quantitative PCR assays to quantify viral load since, as in the case of antibody titre, there appears to be correlation of high viral loads with the likelihood of developing ATL and TSP in HTLV-I carriers.
E. Management
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.
F. Prevention
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.
The illustration on the left shows a schematic of the structure of an HTLV-1 viral particle, or virion. The image above is a transmission electron micrograph HTLV particles adjacent a cell in culture. Images courtesy Mike Lairmore, OSU
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