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      The Prevalence and Significance of HTLV-I/II Seroindeterminate Western Blot Patterns

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          Abstract

          Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15–20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.

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          Origin of the human malaria parasite Plasmodium falciparum in gorillas.

          Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.
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            Origin of the human malaria parasite Plasmodium falciparum in gorillas

            Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here, we used single genome amplification (SGA) strategies to show that wild-living African apes are naturally infected with at least nine Plasmodium species, including one that is the direct precursor of P. falciparum. Among nearly 3,000 ape fecal specimens collected from 57 field sites throughout central Africa, we found Plasmodium spp. infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Panpaniscus). Ape plasmodial infections were highly prevalent, widely distributed, and almost always made up of mixed parasite species. To obtain Plasmodium sequences not confounded by in vitro recombination, we used SGA to amplify fragments of the mitochondrial (956bp of the cytochrome b gene; 3.4kb and 3.3kb half-genome fragments), apicoplast (390bp of the caseinolytic protease C gene) and nuclear (772bp of the lactate dehydrogenase gene) genomes. Among more than 1,100 such sequences from 80 chimpanzee and 55 gorilla samples, we found nine that were related to P. malariae, P. ovale or P. vivax. All others grouped within one of six chimpanzee- or gorilla-specific lineages representing distinct Plasmodium species within the Laverania subgenus. One of these from western gorillas was comprised of parasites that were nearly identical to P. falciparum. In phylogenetic trees of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin, and that all known human strains appear to have resulted from a single cross-species transmission event.
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              The discovery of the first human retrovirus: HTLV-1 and HTLV-2

              I describe here the history leading up to and including my laboratory's discovery of the first human retrovirus, HTLV-I, and its close relative, HTLV-II. My efforts were inspired by early work showing a retroviral etiology for leukemias in various animals, including non-human primates. My two main approaches were to develop criteria for and methods for detection of viral reverse transcriptase and to identify growth factors that could support the growth of hematopoietic cells. These efforts finally yielded success following the discovery of IL-2 and its use to culture adult T cell lymphoma/leukemia cells.
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                Author and article information

                Journal
                Viruses
                Viruses
                Molecular Diversity Preservation International (MDPI)
                1999-4915
                August 2011
                2 August 2011
                : 3
                : 8
                : 1320-1331
                Affiliations
                Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; E-Mails: akahatay@ 123456ninds.nih.gov (Y.A.); JacobsonS@ 123456ninds.nih.gov (S.J.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: abramsan@ 123456mail.nih.gov ; Tel.: +1-301-496-0519; Fax: +1-301-402-0373.
                Article
                viruses-03-01320
                10.3390/v3081320
                3185804
                21994781
                6330af0c-ef7f-43ba-ac21-d81ddbdcad4b
                © 2011 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 13 June 2011
                : 22 July 2011
                : 23 July 2011
                Categories
                Review

                Microbiology & Virology
                seroindeterminate,western blot,htlv-i
                Microbiology & Virology
                seroindeterminate, western blot, htlv-i

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