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H F Liu

Publications and source records attributed to H F Liu.

At least 37 records · Page 2Linked to original sources

The simian T-lymphotropic virus STLV-PP1664 from Pan paniscus is distinctly related to HTLV-2 but differs in genomic organization.

We have isolated a highly divergent simian T-lymphotropic virus, STLV-PP1664, from a wild-caught bonobo (Pan paniscus). Previous phylogenetic analysis suggested that this virus represents an additional type of STLV but this has now become a matter of discussion. We have now obtained and analyzed the entire genome of STLV-PP1664. All major genes and their corresponding viral messengers were identified. Sequence comparison and phylogenetic analysis indicated that this virus, together with the closely related panp isolate, belongs to an early lineage within the PTLV-2 clade, differing from HTLV-2 by about 25%. In contrast to the HTLV-1 and HTLV-2 LTR, only two 21-bp repeats instead of three were found in the STLV-PP1664 LTR. Additional messengers, resulting from alternative splicing, potentially encode five different accessory proteins from open reading frames in the pX region: prorfI, porfII, ptorfV', and two isoforms of Rex. The amino acid sequences of these proteins are only distinctly related to the accessory proteins from HTLV-2. These data suggest a different genomic organization of the STLV-PP1664 pX region than that of HTLV-2. We conclude that STLV-PP1664, although related to HTLV-2, has some distinct features in the LTR and the pX regions, the impact of which needs further investigation. Although arguments pro and contra a distinct classification are nearly equally balanced, we propose to classify this virus as an STLV-2, designated STLV-2PP1664.

Amino Acid Sequence↗

GB virus C: a novel pathogen or a curiosity for virologists?

The recently identified GB virus C is a flavivirus related to the hepatitis C virus. It appears quite prevalent in the general population and especially in individuals at risk of parenteral transmission. Many questions remain, most importantly the pathogenic role of the virus. It is unlikely that this virus has a major role in hepatic disease.

Flaviviridae↗

African origin of human T-lymphotropic virus type 2 (HTLV-2) supported by a potential new HTLV-2d subtype in Congolese Bambuti Efe Pygmies.

We identified a potential new subtype within human T-cell lymphotropic virus type 2 (HTLV-2), HTLV-2d, present in members of an isolated Efe Bambuti Pygmy tribe. Two of 23 Efe Pygmies were HTLV-2 seropositive, with HTLV-2 Western blot and enzyme-linked immunosorbent assay reactivities. From one of them the entire genome of the HTLV-2 strain Efe2 could be amplified and sequenced. In all gene regions analyzed, this strain was the most divergent HTLV-2 strain, differing by 2.4% (tax/rex) to 10.7% (long terminal repeat) from both subtypes HTLV-2a and HTLV-2b, yet major functional elements are conserved. The similarity between the HTLV-2 Efe2 Gag and Env proteins and the corresponding HTLV-2a and -2b proteins is consistent with the observed serological reactivity. In the proximal pX region, one of the two alternative splice acceptor sites is abolished in HTLV-2 Efe2. Another interesting feature of this potential new subtype is that it has a Tax protein of 344 amino acids (aa), which is intermediate in length between the HTLV-2a Tax protein (331 aa) and the HTLV-2b and -2c Tax proteins (356 aa) and similar to the simian T-cell lymphotropic virus type 2 (STLV-2) PP1664 Tax protein. Together these two findings suggest a different phenotype for the HTLV-2 Efe2 strain. Phylogenetic analyses confirmed that the Pygmy Efe2 strain potentially belonged to a new and quite divergent subtype, HTLV-2d. When the STLV-2 bonobo viruses PP1664 and PanP were used as an outgroup, it was clear that the Pygmy HTLV-2 Efe2 strain had the longest independent evolution and that HTLV-2 evolution is consistent with an African origin.

Amino Acid Sequence↗

Molecular analysis of GB virus C isolates in Belgian hemodialysis patients.

GB virus C (GBV-C) has been detected in Belgian hemodialysis patients. To study their genomic diversity and phylogenetic relationship, a 592 nucleotide fragment extending from the 5' non-coding region to part of the E1 gene of the GBV-C genome was amplified and sequenced from 12 Belgian hemodialysis patients in two different centers. Together with strains from different geographical origins, these sequences were analyzed phylogenetically using three different methods. A consistent tree topology was obtained with all methods. Three GBV-C genotypes were observed with two subtypes in type 2 and a questionable subtyping in type 1. Except for one isolate falling into type 1 cluster which mainly consists of African strains, all the other Belgian strains clustered within the type 2a branch. Two GBV-C isolates in two patients from the same hemodialysis center clustered together closely, suggesting a nosocomial transmission. In view of their long branch length, it seems unlikely that the other Belgian strains evolved recently from a common ancestor. Our results indicate that the major type circulating among Belgian hemodialysis patients seems to be 2a, which is usual for Europe and North America, but that the African type 1 also exists to a minor extent. Although patient to patient transmission of GBV-C in Belgian hemodialysis centers did occur, it may not account for the majority of infections.

Base Sequence↗

Use of a generic polymerase chain reaction assay detecting human T-lymphotropic virus (HTLV) types I, II and divergent simian strains in the evaluation of individuals with indeterminate HTLV serology.

In countries with a low prevalence of human T-lymphotropic virus (HTLV) infection, indeterminate HTLV serologies are a major problem in blood bank screening because of the uncertainties about infection in these cases. The recent discovery of two new types of simian T-lymphotropic viruses (STLV), which give an HTLV-indeterminate serology, raises the question whether indeterminate serologies in humans may be linked to new types of HTLV. Starting from a Tax sequence alignment of all available primate T-cell lymphotropic virus strains (PTLV), including the two new types STLV-PH969 and STLV-PP1664, we developed generic and type-specific nested polymerase chain reactions (PCRs). The generic PCR proved to be highly sensitive and cross-reactive for all four types of PTLV, while the discriminatory PCRs had a high sensitivity and a specificity of 100%. There was no cross-reactivity with human immunodeficiency virus (HIV), ensuring correct interpretation of results from coinfected patients. Among the 77 serologically indeterminate samples tested, 6 were found to be HTLV-1 PCR positive and 1 was HTLV-II PCR positive. Sequencing of one of the HTLV-I PCR positives excluded PCR contamination, and revealed a divergent type of HTLV-I. The majority of the seroindeterminate samples (91%) were however HTLV-PCR negative, and no new types of HTLV were found. This new assay can identify otherwise undetected HTLV-I or HTLV-II infections and is a useful tool of screening for new types of HTLV among seroindeterminate samples.

Animals↗

The three human T-lymphotropic virus type I subtypes arose from three geographically distinct simian reservoirs.

To investigate the origin of human T-lymphotropic virus I (HTLV-I), strains of diverse geographical origin were analysed. We sequenced the LTR and env genes of HTLV-I strains from Brazil, Central African Republic, Taiwan and Zaire, and the simian T-lymphotropic virus type I (STLV-I) strain PHSu1 from a baboon from the Sukhumi primate centre. We performed phylogenetic analyses using neighbour-joining, parsimony and maximum likelihood methods. Three separate HTLV-I clusters were identified interspersed between STLV-I clusters. The Brazilian and the Taiwanese strains were within the first well-supported cluster containing all cosmopolitan HTLV-I strains flanked by west African STLV-I strains. The HTLV-I strains from Central African Republic and Zaire fell into a central African cluster close to the chimpanzee STLV-I isolates. The third well-supported cluster included all Melanesian HTLV-I strains and had Indonesian STLV-I strains as closest neighbours. Therefore, currently known HTLV-I strains represent three HTLV-I subtypes that most probably have originated from three geographically distinct interspecies transmission events. The highly divergent PHSu1, isolated from Papio hamadryas, was closely related to PCY-991, isolated from Papio cynocephalus, both from the Sukhumi primate centre. Both clustered together with Asian wild-caught rhesus macaque STLV-I strains suggesting recent interspecies transmission of virus from rhesus macaques to colony-bred African baboons at the Sukhumi primate centre. In the rooted env trees obtained using the STLV strain PH969 as an outgroup, the Asian strains branched off before the African strains, implying an Asian origin for HTLV/STLV type I based on presently available strains.

Animals↗

The presence of a divergent T-lymphotropic virus in a wild-caught pygmy chimpanzee (Pan paniscus) supports an African origin for the human T-lymphotropic/simian T-lymphotropic group of viruses.

We isolated a divergent simian T-lymphotropic virus (STLV) (strain PP1664) from a wild-caught African bonobo (pygmy chimpanzee, Pan paniscus). Molecular and phylogenetic characterization of this virus show that it reliably separates from the two well-established primate T-lymphotropic virus types, HTLV-I/STLV-I (PTLV-I) and PTLV-II, and from a third type isolated from an African-born Papio hamadryas and designated by us as PTLV-L. Four of eight bonobos kept at the Antwerp Zoo, Belgium, showed an aberrant PTLV serology. We amplified and sequenced a 709 bp PTLV proviral tax/rex fragment from one of the reactive bonobos. It differs by about 25 % from the homologous nucleotide sequences of PTLV-I and PTLV-L and by about 17 % from PTLV-II. This is comparable to the differences among the three known types. Including the most divergent STLV-I strains sequenced to date, for example, strain PHSu1 sequenced here, the divergence in this region within PTLV-I is less than 11 % and within PTLV-II less than 4%. Although very divergent, this new bonobo STLV is the closest well-characterized simian relative of HTLV-II, raising the possibility of very divergent new HTLV strains. Our results show that the number of PTLV types should be considered open and that the variety of indigenous viruses in the PTLV group is greatest in Africa. Thus, as for the other primate retroviruses HIV and SIV, PTLV most probably has its origins in Africa.

Africa↗

HTLV-negative and HTLV type I-positive tropical spastic paraparesis in northeastern Brazil.

A type-specific serological survey among 1042 random nonneurological outpatients in two cities in the state of Ceara (northeastern Brazil) shows a low prevalence of HTLV-I (0.34% in Fortaleza; 0.44% in Crato) and of HTLV-II (0.34% in Fortaleza; 0% in Crato). Among 62 chronic myelopathic patients seen in Fortaleza 27 patients were found with clinical features of tropical spastic paraparesis (TSP); 10 of 27 were found HTLV-I seropositive (37%; 95% confidence limits, 19-58%). Proviral genome detection by polymerase chain reaction in 5 seropositive and 12 seronegative patients confirmed the serological findings. This excludes HTLV-I or -II infection as a cause in the seronegative TSP patients. The HTLV-positive and -negative patients did not differ clinically and by history, except that seropositives had a longer mean disease duration, a female predominance, and a higher proportion of white Caucasians. In this population with low HTLV-I and HTLV-II prevalences, HTLV-negative TSP is at least as frequent as the HTLV-I-associated TSP.

Brazil↗

Mammalian topoisomerase I has base mismatch nicking activity.

The all-type nicking enzyme (ATE) from human HeLa cells or calf thymus can nick DNA at the first phosphodiester bond 5' to all 8 possible mismatched bases. The strand disparity of this nicking is influenced by the neighboring nucleotide sequences. After nicking, the ATE covalently binds to the 3' end of the DNA product to form a cleavable complex, whose formation is insensitive to camptothecin, a specific inhibitor of eukaryotic topoisomerase I (Topo-I). During the purification of ATE from calf thymus, a Mg(2+)-independent relaxation activity, characteristic of eukaryotic Topo-I, copurifies with the mismatch-nicking activity. The ATE from calf thymus may be a breakdown product of Topo-I. N-terminal amino acid analysis indicates that one of the polypeptides with ATE activity contains the C-terminal portion of Topo-I. Moreover, active human Topo-I, expressed as a fusion protein in Escherichia coli, is also capable of nicking all 8 base mispairs in the absence of Mg2+. This mismatch-specific nicking activity may be a novel property of the mammalian Topo-I.

Animals↗

A primate T-lymphotropic virus, PTLV-L, different from human T-lymphotropic viruses types I and II, in a wild-caught baboon (Papio hamadryas).

Searching for clues to the evolution of the primate T-lymphotropic viruses (PTLVs), which include the human and the simian T-lymphotropic viruses (HTLV and STLV), we have identified another PTLV, which differs sufficiently from the known PTLV-I and PTLV-II types to be designated here PTLV-L. The virus was isolated from a wild-born baboon (Papio hamadryas) from Eritrea. In a cDNA library a 1802-bp-long fragment was identified that extends from the env region, including the complete transmembrane protein gene, to part of the tax/rex gene. Homologies at the nucleotide sequence level of PTLV-L, prototype simian T-lymphotropic virus-PH969, with HTLV-I and -II, respectively, were 62% and 64% overall, 65% and 70% in the env region, and 80% and 80% in the partial tax/rex sequence. In the 5' part of the pX region a significant homology was seen only with HTLV-II (52%). Phylogenetic analysis based on the gene encoding the transmembrane protein indicates that PTLV-L represents a PTLV type with a long independent evolution, longer than any strain within the PTLV-I or PTLV-II groups. The finding of another PTLV type in African baboons is further evidence of the wide variety of PTLV found on this continent. Whether PTLV-L resembles PTLV-I and PTLV-II in the extension of its host range to other primates, including humans, remains to be seen.

Amino Acid Sequence↗

Primate T-lymphotropic virus type I LTR sequence variation and its phylogenetic analysis: compatibility with an African origin of PTLV-I.

Due to the low evolutionary rate and the limited horizontal transmission of human T-lymphotrophic virus type I (HTLV-I), its phylogenetic analysis reveals the movements and contacts of ancient populations. Since simian strains cannot be distinguished from human strains by phylogenetic criteria, this virus has appropriately been called primate T-lymphotropic virus type I (PTLV-I). We sequenced the LTR of six PTLV-I strains: three HTLV-I strains from African patients with tropical spastic paraparesis (TSP) (Equateur, Zaire), two laboratory HTLV-I strains of Japanese origin, MT-2 and MT-4, and one STLV-I from a baboon of the primate center in Sukhumi, Georgia. We applied four phylogenetic inference methods: neighbor-joining (NJ), unweighted pair group method using arithmetic averages (UPGMA), Fitch and Wagner parsimony (pars), and maximum likelihood (ML), to these 6 LTR sequences and 18 published LTR sequences (cosmopolitan, African, and Melanesian HTLV-I strains and African and Asian STLV-I strains). Three major HTLV-I subtypes can be identified with all four methods: the cosmopolitan HTLV-Ia, the central African HTLV-Ib, clearly descendant from a STLV-I CH-like African ancestral simian strain, and the Melanesian HTLV-Ic, probably descendant from an Asian STLV-I strain. We observe a segregation of PTLV-I sequences according to their geographical origin and not according to host species. The Zairean strains form a cluster closely related to an STLV-I strain isolated from a chimpanzee (STLV-I CH) and distinct from western African strains, which belong to the cosmopolitan subtype of HTLV-I. The Sukhumi STLV-I strain found in a captive-born baboon was of Asian descent. We experienced rooting problems with UPGMA when using HTLV-II as an outgroup. Concordant results with all four methods were obtained by eliminating HTLV-II LTR sequence fragments with bad alignment to HTLV-I. This resulted in a HTLV-II root node on the African STLV-I TAN90 terminal branch (with bootstrap values above 92% for the NJ and pars methods) and not on the Asian STLV-I PtM3 branch, as has been derived by others based on their use of UPGMA. The results of the analyses also support a higher evolutionary rate of PTLV-I in Asia, implying that the trees obtained with the NJ and ML methods have a higher reliability. These results are more compatible with an ancient African origin of PTLV-I than with an Asian origin.

Africa↗

Familial transmission and minimal sequence variability of human T-lymphotropic virus type I (HTLV-I) in Zaire.

Our group previously reported a strong familial clustering of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Zaire, suggesting a familial transmission of the virus together with the presence of cofactors. In the present study among 84 relatives of 16 HTLV-I-positive or HAM/TSP index cases, we found that all 15 seropositive children had a seropositive mother and that all 15 children with a seropositive father but a seronegative mother were seronegative. Lymphocytes of 17 relatives from 2 families with a familial HTLV-I-associated neuropathy were tested in 2 polymerase chain reaction (PCR) assays amplifying pol and tax/rex gene fragments. The 10 seropositive individuals were PCR positive for HTLV-I and the 7 seronegatives were negative in both PCR assays. The PCR results showed no evidence for a long lag period between infection with HTLV-I and seroconversion. The HTLV-I long terminal repeat (LTR) of these 10 individuals, related in the first to the fourth degree, was amplified and sequenced. Identical sequences were found within the families except for one woman infected with two variants, one being the familial strain and the other a mutated one with a single nucleotide substitution in the 755 sequenced nucleotides of the LTR region. The family strain and the mutant were both present in two samples taken 1 year apart. Together, the HTLV-I serology, PCR, and sequencing results point toward mother-to-child transmission as the main mode of HTLV-I infection in this population. Comparison of the LTR sequences of the two families with other HTLV-I strains from different geographical regions shows that the Zairean HTLV-I strains form a separate cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[P21 expression of ras oncogene product in benign and malignant female mammary lesions].

The level of P21 protein in 40 breast carcinomas, 37 benign tumors and 52 proliferative breast diseases in females were determined by the ABC immunohistochemical method. The positive rate was 72.5%, 32.43% and 23.07% respectively. The positive expressions were mainly found in tumor cells in poorly differentiated infiltrating ductal carcinomas and in 3 of the 5 proliferative breast disease cases with atypical hyperplasia of ductal epithelium, suggesting that P21 protein detection could provide a molecular biological basis for the evaluation of malignant changes and the prognosis of mammary lesions.

Breast Neoplasms↗

[An animal model for testing hypoglycemic and hypolipidemic drugs].

A new animal model of hyperglycemia and hyperlipidemia was established by treating normal Kunming mice with alloxan (iv). After different time intervals, the levels of blood glucose (BG) and serum triglyceride (TG) were determined. Forty-eight h after alloxan administration, the BG increased significantly, and the level of serum triglyceride reached maximum. The levels of blood glucose, serum triglyceride, cholesterol (CHOL) and free fatty acid (FFA) for vehicle treated mice were about 3.1, 4.0, 1.1, and 1.7 times those of normal Kunming mice, respectively. To evaluate the new animal model, four drugs were used. Two of them were antihyperglycemic drugs, metformin and a Recipe of Chinese Herbs (RCH). The other two were antihyperlipidemic agents, clofibrate and fenofibrate. All drugs showed positive effects on this kind of alloxan-diabetic Kunming mice. It can be concluded that this kind of alloxan-treated Kunming mice is useful for testing hypoglycemic and hypolipidemic drugs.

Animals↗

HTLV-II seroprevalence in pygmies across Africa since 1970.

HTLV-II-specific antibodies, with patterns similar to those in the Americas, were present in sera collected about 1970 from Bambuti pygmies in Zaire (14/102; 14%) and from pygmies in Cameroon (5/214; 2.3%), and were more prevalent than HTLV-I. In the Central African Republic, 504 pygmies were HTLV negative. After finding of 4 HTLV-II seropositives among 12 Bambuti pygmies sampled in 1991, this established that HTLV-II or a related retrovirus is present as an ancient endemic in some, but not all, insulated groups of African pygmies, similar to the HTLV-II distribution in Amerindian populations. The endemic among the oldest inhabitants of central Africa, and the occasional and scattered occurrence of apparent HTLV-II among predominant HTLV-I in other Africans, fit well with an ancient African virus and not with importation from the New World. Theories on the origin and evolution of the primate T-lymphotropic viruses (PTLVs) should take into account the longstanding presence of HTLV-II-type viruses in both the Old and New World. Present serology suggests identity of the African viruses with HTLV-II, but their assignment to a new HTLV type is open should genetic analysis show strong divergence from American HTLV-II. Clinical expression, if any, remains to be studied.

Blotting, Western↗