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Human adenovirus (HAdV) serotype 14 is rarely identified. However, an emerging variant, termed HAdV-14p1, recently has been described in the United States in association with outbreaks of acute respiratory disease [...]

Adult T-cell leukemia-lymphoma (ATLL) is a group of T-cell malignancies caused by infection with human T-lymphotropic virus type I (HTLV-I). Although the pathogenesis of ATLL remains incompletely understood, the viral regulatory protein Tax is centrally involved in cellular transformation. Here we describe the generation of HTLV-I Tax transgenic mice using the Lck proximal promoter to restrict transgene expression to developing thymocytes. After prolonged latency periods, transgenic mice developed diffuse large-cell lymphomas and leukemia with clinical, pathological and immunological features characteristic of acute ATLL. Transgenic mice were functionally immunocompromised and they developed opportunistic infections. Fulminant disease also developed rapidly in SCID mice after engraftment of lymphomatous cells from transgenic mice. Flow cytometry showed that the cells were CD4[sup.-] and CD8[sup.-], but CD44[sup.+], CD25[sup.+] and cytoplasmic CD3[sup.+]. This phenotype is indicative of a thymus-derived pre-T-cell phenotype, and disease development was associated with the constitutive activation of NF-[kappa]B. Our model accurately reproduces human disease and will provide a tool for analysis of the molecular events in transformation and for the development of new therapeutics., Author(s): Hideki Hasegawa [1, 2, 8]; Hirofumi Sawa [3, 4, 8]; Martha J Lewis [2, 5]; Yasuko Orba [3]; Noreen Sheehy [2]; Yoshie Yamamoto [6]; Takeshi Ichinohe [1]; Yasuko Tsunetsugu-Yokota [...]

The primary function of the HIV-1 regulatory protein Tat, activation of transcription from the viral LTR, is highly regulated by complex interactions between Tat and a number of host cell proteins. Tat nuclear import, a process mediated by importin [beta], is a prerequisite for its activity. Here, we report and characterize the interaction of the human inhibitor of MyoD family domain-containing protein (I-mfa), HIC, with Tat at a biochemical and a functional level. This interaction was shown to occur in vivo and in vitro and to involve the nuclear localization signal and the transactivation responsive element-binding domains of Tat and the I-tufa domain of HIC. Coexpression of HIC and Tat resulted in the down-regulation of transactivation of the HIV-1 LTR, and colocalization studies revealed the cytoplasmic sequestration of Tat by HIC. Functionally this sequestration appears to be the underlying mechanism of LTR transcriptional repression by HIC and represents a unique mechanism for the control of Tat activity and regulation of HIV-1 replication. NLS | protein-protein interaction | nuclear import

The results of seroepidemiologic studies of human T-lymphotropic virus type-I and type II infections in different population groups in Argentina are presented. The studies have shown a high prevalence of human T-lymphotropic virus type-I and type II infection in the blood donors in the provinces in the north of Argentina and a low prevalence in the provinces in the central region of the country.

Although HIV type 1 (HIV-1) cannot efficiently replicate in simian cells, the mechanism(s) involved in the restriction of virus tropism remain unclear. To investigate this, we have focused on the identification of human cellular factors that can influence the infectivity of HIV-1 derived from African green monkey producer cells. Whereas the infectivity of HIV-1 derived from such cells was only 10-15% of that of human cell-derived virus, expression of human topoisomerase I in the African green monkey cells resulted in a 5-fold increase of the infectivity of progeny HIV-1 virions. Replacement of glutamate-236 and asparagine-237 of human topoisomerase I with the corresponding residues (aspartate and serine, respectively) of the African green monkey enzyme abolished this enhancement of HIV-1 infectivity. This positive effect of human topoisomerase I expression in the African green monkey producer cells seemed to result from the promotion of HIV-1 cDNA synthesis. Thus, human topoisomerase I plays an important role in HIV-1 replication and infectivity, and differences in the species specificity of HIV-1 infection can at least in part be attributed to differences in topoisomerase I activities. African green monkey | simian

Molecular characterization of human T-cell lymphotropic virus II (HTLV-II) isolates in North America and Europe has shown the existence of two principal subtypes of the virus, HTLV-IIa and HTLV-IIb. Subsequent studies on HTLV-II isolates from Brazil have suggested the existence of a unique variant phylogenetically related to HTLV-IIa but phenotypically similar to HTLV-IIb with respect to the transactivatory protein, Tax. This variant has been designated HTLV-IIc. To better clarify the variability and distribution of HTLV-II in Brazil, the viruses present in two population groups from the Amazon region were tested for the presence of HTLV-II using serological and molecular assays. The groups consisted of blood donors from three Amerindian communities and of HIV-l/HTLV-II coinfected patients residing in Belem, an urban area. Nucleotide sequences and phylogenetic analysis confirmed the presence of HTLV-IIc subtype among Amerindian populations and, for the first time, the presence of the same virus among urban groups in Belem. The iso]ated occurrence of the HTLV-IIc subtype among Amerindian populations in the Amazon region could be attributed to (1) the different migratory pathways and founder effect, or (2) the local origin of a proto-HTLV-II carried by Amerindian ancestors who migrated to the Amazon circa 11,000 to 13,000 years ago. These results suggest that not only is HTLV-IIc unique to this region, but that its presence in urban areas of Brazil has resulted from admixture processes during the colonization of the country. KEY WORDS: HTLV-II, NUCLEOTIDE SEQUENCE ANALYSIS. PHYLOGENETIC ANALYSIS, AMERINDIAN POPULATIONS, Human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II) are members of the family Retroviridae and share several molecular and biological properties (Hall et al. 1994a). HTLV-I is [...]

Byline: S. Ijichi (1), Naomi Ijichi (1), Yoshihisa Yamano (2), William W. Hall (3), Mitsuhiro Osame (2) Keywords: Key wordsaHuman T lymphotropic virus type I; HTLV-I-associated myelopathy/tropical spastic paraparesis; Quasispecies Abstract: aTo understand the mechanisms involved in the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), three in vivo phenomena which have been observed in the peripheral blood of patients and differing from that in asymptomatic HTLV-I carriers must be taken into consideration: (a) the presence of increased HTLV-I viral load, (b) a higher immune responsiveness against HTLV-I antigens, and (c) biased nucleotide substitutions in the HTLV-I pX region which indicate a decreased selection pressure for viral amino acid changes. We now propose a hypothesis which focuses on the in vivo dynamics of HTLV-I infected lymphocyte migration and which incorporates these features. In addition, the hypothesis assumes the existence of a deviation in immune surveillance for HTLV-I in the central nervous system (CNS) in spite of the presence of frequent specific immune effectors. We suggest that in the active phase of HAM/TSP, accompanied with or following autoaggressive interactions between infected lymphocytes and immunocompetent cells in the CNS, there is a consequential reflux of the infected lymphocytes to the peripheral blood. The reflux of infected cells would be expected to provide peripheral blood with tissue-derived HTLV-I proviruses which have been indulged and propagated in an immune-privileged site. This process would result in and account for the observed increase in viral load and the substitution bias in HTLV-I sequences in the peripheral blood. Author Affiliation: (1) Nagahama Shinryojyo, 546 Nagahama, Shimokoshiki-mura, Satsuma-gun, Kagoshima 896--14, Japan, JP (2) Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8--35--1 Sakuragaoka, Kagoshima 890, Japan, JP (3) Department of Medical Microbiology, University College Dublin, Belfield, Dublin 4, Ireland, IE Article note: Received: 31 January 1997 / Accepted: 17 June 1997

A procedure is described for rapid, high-confidence identification of proteins using matrix-assisted laser desorption/ionization tandem ion trap mass spectrometry in conjunction with a genome database searching strategy. The procedure involves excision of copper-stained bands or spots from electrophoretic gels, in-gel trypsin digestion of the proteins, single-stage mass spectrometric analysis of the resultant mixture of tryptic peptides, followed by tandem ion trap mass spectrometric analysis of selected individual peptides, and database searching of the relevant genomic database using the program PepFrag. The scheme provides sensitive, real-time protein identification as well as facile identification of modifications. A single operator can unambiguously identify 5-10 proteins/day from an organism whose genome is known at a level of >0.5 pmol of protein loaded on a gel. The utility of the technique was demonstrated by the identification and characterization of a band from a human HTLV-I preparation and 11 different proteins from a yeast RNA polymerase II C-terminal repeat domain-affinity preparation. The technology has great potential for postgenome biological science, where it promises to facilitate the dissection and anatomy of macromolecular assemblages, the definition of disease state markers, and the investigation of protein targets in biological processes such as the cell cycle and signal transduction.

A study has been conducted to examine the association between HIV-1 gag proteins and topoisomerase I activity during the reverse transcription of viral RNA. Construction of recombinant vaccinia viruses revealed that the nucleocapsid protein 15 and not the gag protein which enhances the activity of topo I. It was also shown that topo I enhanced HIV-1 reverse transcriptase activity in vitro. These results suggest that topo I plays a critical role in the reverse transcription of HIV-1 RNA.

THE CUTANEOUS T CELL LYMPHOMAS (CTCLs) are a group of rare disorders that include mycosis fungoides Sezary syndrome, Woringer-Kolopp disease, and adult T cell leukemia/lymphoma (ATL) [1]. ATL is an [...]

The value of Alfred D. Chandler Jr.'s fit-performance directive in organizational research is analyzed.

The phylogeny of human T cell lymphotropic virus type II (HTLV-II) was investigated by using strains isolated from Amerindian and Pygmy tribes, in which the virus is maintained primarily through mother-to-child transmission via breast-feeding, and strains from intravenous drug users (IDUs), in which spread is mainly blood-borne via needle sharing. Molecular clock analysis showed that HTLV-II has two different evolutionary rates with the molecular clock for the virus in IDUs ticking 150-350 times faster than the one in endemically infected tribes: 2.7 x [10.sup.-4] compared with 1.71/7.31 x [10.sup.-7] nucleotide substitutions per site per year in the long terminal repeat region. This dramatic acceleration of the evolutionary rate seems to be related with the mode of transmission. Mathematical models showed the correlation of these two molecular clocks with an endemic spread of HTLV-II in infected tribes compared with the epidemic spread in IDUs. We also noted a sharp increase in the population size of the virus among IDUs during the last decades probably caused by the worldwide increase in intravenous drug use.

Author(s): Anne-Mieke Vandamme [1]; William W. Hall [2]; Martha J. Lewis [2]; Patrick Goubau [3]; Marco Salemi [1] To the editor Li et al. describe the presence of HTLV-I proviral [...]