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1.
Proc Natl Acad Sci U S A ; 117(22): 12222-12229, 2020 06 02.
Article in English | MEDLINE | ID: mdl-32430331

ABSTRACT

With very little direct biological data of HIV-1 from before the 1980s, far-reaching evolutionary and epidemiological inferences regarding the long prediscovery phase of this pandemic are based on extrapolations by phylodynamic models of HIV-1 genomic sequences gathered mostly over recent decades. Here, using a very sensitive multiplex RT-PCR assay, we screened 1,645 formalin-fixed paraffin-embedded tissue specimens collected for pathology diagnostics in Central Africa between 1958 and 1966. We report the near-complete viral genome in one HIV-1 positive specimen from Kinshasa, Democratic Republic of Congo (DRC), from 1966 ("DRC66")-a nonrecombinant sister lineage to subtype C that constitutes the oldest HIV-1 near full-length genome recovered to date. Root-to-tip plots showed the DRC66 sequence is not an outlier as would be expected if dating estimates from more recent genomes were systematically biased; and inclusion of the DRC66 sequence in tip-dated BEAST analyses did not significantly alter root and internal node age estimates based on post-1978 HIV-1 sequences. There was larger variation in divergence time estimates among datasets that were subsamples of the available HIV-1 genomes from 1978 to 2014, showing the inherent phylogenetic stochasticity across subsets of the real HIV-1 diversity. Our phylogenetic analyses date the origin of the pandemic lineage of HIV-1 to a time period around the turn of the 20th century (1881 to 1918). In conclusion, this unique archival HIV-1 sequence provides direct genomic insight into HIV-1 in 1960s DRC, and, as an ancient-DNA calibrator, it validates our understanding of HIV-1 evolutionary history.


Subject(s)
Cell Lineage/genetics , Evolution, Molecular , Genetic Variation , Genome, Viral , HIV Infections/genetics , HIV-1/genetics , Paraffin Embedding/methods , Adult , Democratic Republic of the Congo , HIV Infections/virology , Humans , Male , Phylogeny , Sequence Analysis, DNA , Time Factors
2.
Pediatr Hematol Oncol ; 32(4): 239-49, 2015 May.
Article in English | MEDLINE | ID: mdl-25871614

ABSTRACT

BACKGROUND: Information on presentation and outcome of pediatric non-Hodgkin's lymphoma is limited from Africa. The demographic characteristics, distribution of different subtypes were noted and compared with published reports from other parts of the world. METHODS: The study was conducted in Kinshasa, the Democratic Republic of Congo between January 2002 and December 2012. RESULTS: A total of 63 cases of pediatric non-Hodgkin's lymphoma were retrospectively analyzed. This cohort represents the largest series of pediatric non-Hodgkin's lymphoma presented from sub-Saharan Africa. Median age was 8.7±3.6 years. There were 43 (68.3%) males. A mean of 82 ± 59 days passed from detection of the first sign to referral to oncology unit. Morphology distribution showed that 42 cases (66.7%) had a diagnosis of Burkitt lymphoma, 16 cases (25.4%) had diffuse large B-cell lymphoma and 5 cases (7.9%) had NHL-not otherwise specified. The majority of patients (82.5%) had advanced stage (stage III and IV). Immunohistochemistry findings were available for 32 biopsy samples. All (100%) cases were B-cell non-Hodgkin's lymphoma and immunohistochemistry had identified 18 (56.3%) cases of Burkitt lymphoma. In our cohort, 22 of 32 cases expressed positive bcl-2 and 12 (37.5%) were found to be positive for bcl-6. Thirty-one (96.7%) cases were positive for high Ki-67 antigen expression. Assuming that cases lost to follow-up worsened and died, the mortality would be 98.4%. CONCLUSION: In comparison to western data, we observed higher proportion of B-cell non-Hodgkin's lymphoma, Burkitt Lymphoma and patients with bcl-2 expression.


Subject(s)
DNA-Binding Proteins/biosynthesis , Lymphoma, Non-Hodgkin , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Adolescent , Africa, Central/epidemiology , Child , Child, Preschool , Female , Humans , Lymphoma, Non-Hodgkin/epidemiology , Lymphoma, Non-Hodgkin/metabolism , Lymphoma, Non-Hodgkin/pathology , Male , Proto-Oncogene Proteins c-bcl-6 , Sex Factors
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