Hong Lou

The presence of ancient human T-cell lymphotropic virus type I provirus DNA in an Andean mummy

The worldwide geographic and ethnic clustering of patients with diseases related to human T-cell lymphotropic virus type I (HTLV-I) may be explained by the natural history of HTLV-I infection. The genetic characteristics of indigenous people in the Andes are similar to those of the Japanese, and HTLV-I is generally detected in both groups. To clarify the common origin of HTLV-I in Asia and the Andes, we analyzed HTLV-I provirus DNA from Andean mummies about 1,500 years old. Two of 104 mummy bone marrow specimens yielded a band of human β-globin gene DNA 110 base pairs in length, and one of these two produced bands of HTLV-I-pX (open reading frame encoding p40x, p27x) and HTLV-I-LTR (long terminal repeat) gene DNA 159 base pairs and 157 base pairs in length, respectively. The nucleotide sequences of ancient HTLV-I-pX and HTLV-I-LTR clones isolated from mummy bone marrow were similar to those in contemporary Andeans and Japanese, although there was microheterogeneity in the sequences of some mummy DNA clones. This result provides evidence that HTLV-I was carried with ancient Mongoloids to the Andes before the Colonial era. Analysis of ancient HTLV-I sequences could be a useful tool for studying the history of human retroviral infection as well as human prehistoric migration.

Green Tea Polyphenols Induce Apoptosis in vitro in Peripheral Blood T Lymphocytes of Adult T-Cell Leukemia Patients

Green tea polyphenols (TEA) are known to exhibit antioxidative activity as well as tumor‐suppressing activity. In order to examine the tumor‐suppressing activity of TEA against adult T‐cell leukemia (ATL), we cultivated peripheral blood T lymphocytes of ATL patients (ATL PBLs), an HTLV‐I‐infected T‐cell line (KODV) and healthy controls (normal PBLs) for 3 days in the presence of TEA and its main constituent, epigallocatechin‐3‐gallate (EGCg), to measure cell proliferation and apoptosis, and to quantitate mRNAs of HTLV‐I pX and β‐actin genes of the cultured cells. Growth of ATL PBLs was significantly inhibited by 9–27 μg/ml of TEA and EGCg, in contrast to minimal growth inhibition of T cells of normal PBLs. Inhibition of KODV was intermediate between ATL PBLs and normal PBLs. The ATL PBLs and KODV treated with 27 μg/ml of either TEA or EGCg induced apoptotic DNA fragmentation, producing terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling (TUNEL)‐positive cells, while the normal PBLs treated with the same concentration of TEA or EGCg produced a negligibly small number of TUNEL‐positive cells, in which apoptotic DNA fragmentation was not detectable. Expression of HTLV‐I pX mRNA was suppressed more than 90% in ATL PBLs by treatment with 3–27 μg/ml of either TEA or EGCg, while expression of β‐actin mRNA was much less suppressed by treatment with the same concentration of TEA or EGCg. These results indicate that TEA and EGCg inhibit growth of ATL PBLs, as well as HTLV‐I‐infected T‐cells, by suppressing HTLV‐I pX gene expression and inducing apoptotic cell death.

Characteristic distribution of HTLV type I and HTLV type II carriers among native ethnic groups in South America.

To confirm the geographic and ethnic segregation of HTLV-I and HTLV-II carriers in native populations in South America, we have conducted a seroepidemiological study of native populations in South America, including HTLV-I carriers distributed among seven ethnic groups in the Andes highlands of Colombia, Peru, Bolivia, Argentina, and Chile, and two ethnic groups on Chiloe Island and Easter Island; and HTLV-II carriers distributed among seven ethnic groups of the lowlands along the Atlantic coast of Colombia, Orinoco, Amazon, and Patagonia, and one ethnic group on Chiloe Island. The incidence rate of HTLV-I and HTLV-II carriers varied among the ethnic groups, ranging from 0.8 to 6.8% for HTLV-I seropositivity and from 1.4 to 57.9% for HTLV-II seropositivity. A new HTLV-I focus was found among the Peruvian Aymara (1.6%), the Bolivian Aymara (5.3%) and Quechua (4.5%), the Argentine Puna (2.3%), and the Chilean Atacama (4.1%), while on HTLV-II focus was found among the Brazilian Kayapo (57.9%), the Paraguayan Chaco (16.4%), and the Chilean Alacalf (34.8%) and Yahgan (9.1%). The distribution of HTLV-I/II foci showed a geographic clustering of HTLV-I foci in the Andes highlands and of HTLV-II foci in the lowlands of South America. It was thus suggested that South American natives might be divided into two major ethnic groups by HTLV-I and HTLV-II carrier state.

Search for human T-lymphotropic virus type I carriers among northeastern Chinese

Human T-lymphotropic virus type I (HTLV-I) is thought to be the causative agent of adult T-cell leukemia/ lymphoma (ATL). This virus infection is endemic in southwestern Japan, parts of Africa and the Caribbean Islands. We examined sera of 1645 subjects of Liaoning province, northeastern China to detect HTLV-I carriers in an effort to reveal the migratory route taken by the early Japanese (Jomon people). As a result, all sera were found to be negative as tested by particle-agglutination (PA), immunofluorescence (IF), enzyme-linked immunoabsorbent (ELISA) and Western blotting methods. This suggests that the Jomon people, who are thought to have brought HTLV-I to the Japan archipelago tens of thousands of years ago, did not come from northeast China.

HLA Types and Immune Reaction

Los antigenos leucocitarios (HLA) estan vinculados por genes altamente polimorficos, con el complejo mayor de histocompatibilidad localizando en el brazo corto del cromosoma 6. Dos contingentes distintos del gen del HLA se heredan de los padres en forma mendeliana y que se expresan codominantemente para producir dos sets de antigenos de HLA: A, B-C, DR y DQ, asi como los fenotipos complementarios. El tipo de HLA y los haplotipos son utiles para la identificacion individual y/o grupos geneticos en los seres humanos. Otra importante funcion de la diversidad del HLA es el reconocimiento inmunologico de los antigenos propios o ajenos. Los autoantigenos originados en celulas autologas y los antigenos de origen exogenos son procesados en proteosomas para degradarlos a fragmentos peptidicos los que encajan especialmente de acuerdo a la particular configuracion de las moleculas de HLA. Los complejos HLA peptidicos son reconocidos por un repertorio de linfocitos T o B que expresan una respuesta inmune especifica. Las celulas T y B que reconocen antigenos autologos son naturalmente destruidas, mientras que aquellas celulas expuestas a los antigenos exogenos sobreviven largamente y producen una respuesta amnestica contra los mismos antigenos. Algunas celulas T pueden sobrevivir mas de 30 anos. Asi, la memoria inmune a las celulas T o B es util para la busqueda de antiguas epidemias de enfermedades infecciosas sobrepasada por los distintos grupos etnicos. En ese sentido el estudio de HLA entre los andinos, asi como los antecedentes que se refieren a su susceptibilidad por las infecciones por HTLV 1 son semejantes a las que expresan los japoneses del sur.