Molecular Investigation of Transmission of Human Immunodeficiency Virus Type 1 in a Criminal Case

Retrovirus Laboratory, Department of Virology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Clinical and Diagnostic Laboratory Immunology (Impact Factor: 2.51). 10/2001; 8(5):884-90. DOI: 10.1128/CDLI.8.5.884-890.2001
Source: PubMed

ABSTRACT Very few criminal cases involving human immunodeficiency virus type 1 (HIV-1) transmission have been described. We report on an HIV-1 transmission case with a child being infected by an HIV-1-positive man. The objective was to determine through molecular epidemiology and phylogenetic analyses whether HIV-1 from the HIV-1-positive man could be the source of infection in the HIV-1-positive child, as claimed by the authorities. We conducted genetic analysis of three different parts of the HIV-1 genome (gag, pol, and env) by PCR, direct-sequencing, and phylogenetic analyses. We used maximum likelihood, maximum parsimony, and neighbor-joining methods for the phylogenetic analyses to investigate whether the sequences from the man and the child were related. We found that the viral sequences from the man and the child formed separate clusters in all of the phylogenetic analyses compared to the local controls. A unique amino acid deletion was identified in the C2-V3-C3 region of the env gene in the virus from the man and the child. These results were used in the criminal court to elucidate whether the virus from the man was related to the virus from the child. In summary, the results from the phylogenetic analyses, the sequence distances between the virus from the man and the virus from the child, and the identification of the unique molecular fingerprint in the env gene together indicated that the virus from the man and the virus from the child were epidemiologically linked.

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Available from: Claus Nielsen, Sep 27, 2015
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    • "Molecular epidemiology analyses of rapidly evolving microorganisms have to be framed within evolutionary theory since only this provides the necessary concepts to ascertain proximal and distal relatedness from the observed genetic variation [18,19]. These principles have been successfully applied in previous cases of HIV transmission brought to courts [4,7,20,21] and to many other cases of HIV and HCV transmissions that did not lead to legal investigations [2,5,22-24]. However, none of these involved the investigation and analysis of a large number of potential recipients of the virus from the same source, which continued evolving during the long period in which infections occurred in the case considered here. "
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    ABSTRACT: Molecular phylogenetic analyses are used increasingly in the epidemiological investigation of outbreaks and transmission cases involving rapidly evolving RNA viruses. Here, we present the results of such an analysis that contributed to the conviction of an anesthetist as being responsible for the infection of 275 of his patients with hepatitis C virus. We obtained sequences of the NS5B and E1-E2 regions in the viral genome for 322 patients suspected to have been infected by the doctor, and for 44 local, unrelated controls. The analysis of 4,184 cloned sequences of the E1-E2 region allowed us to exclude 47 patients from the outbreak. A subset of patients had known dates of infection. We used these data to calibrate a relaxed molecular clock and to determine a rough estimate of the time of infection for each patient. A similar analysis led to an estimate for the time of infection of the source. The date turned out to be 10 years before the detection of the outbreak. The number of patients infected was small at first, but it increased substantially in the months before the detection of the outbreak. We have developed a procedure to integrate molecular phylogenetic reconstructions of rapidly evolving viral populations into a forensic setting adequate for molecular epidemiological analysis of outbreaks and transmission events. We applied this procedure to a large outbreak of hepatitis C virus caused by a single source and the results obtained played a key role in the trial that led to the conviction of the suspected source.
    BMC Biology 07/2013; 11(1):76. DOI:10.1186/1741-7007-11-76 · 7.98 Impact Factor
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    • "Phylogenetic analyses have been increasingly used in attempts to clarify epidemiological relationships of HIV-1 infected patients (Abecasis et al., 2011; Albert et al., 1994; Arnold et al., 1995; Banaschak et al., 2000; Birch et al., 2000; Blanchard et al., 1998; de Oliveira et al., 2006; Goujon et al., 2000; Holmes et al., 1993; Leitner, 2000; Leitner et al., 1996; Lemey et al., 2005b; Lemey and Vandamme, 2005; Machuca et al., 2001; Metzker et al., 2002; Ou et al., 1992; Pistello et al., 2004; Salzberger et al., 2000; Yirrell et al., 1997), but there is a continuing discussion about their validity because convergent evolution and transmission of minor HIV variants may obscure epidemiological patterns (Lemey et al., 2005a). In this study we used multiple HIV-1 sequences datasets to compare the sensitivity of molecular epidemiology techniques – phylogenetic analysis methods and various phylogenetic programs – to correctly reconstruct epidemiological relationships among HIV-1 infected patients with different methods. "
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    ABSTRACT: Phylogenetic analysis has been extensively used as a tool for the reconstruction of epidemiological relations for research or for forensic purposes. It was our objective to assess the sensitivity of different phylogenetic methods and various phylogenetic programs to reconstruct epidemiological links among HIV-1 infected patients that is the probability to reveal a true transmission relationship. Multiple datasets (90) were prepared consisting of HIV-1 sequences in protease (PR) and partial reverse transcriptase (RT) sampled from patients with documented epidemiological relationship (target population), and from unrelated individuals (control population) belonging to the same HIV-1 subtype as the target population. Each dataset varied regarding the number, the geographic origin and the transmission risk groups of the sequences among the control population. Phylogenetic trees were inferred by neighbor-joining (NJ), maximum likelihood heuristics (hML) and Bayesian methods. All clusters of sequences belonging to the target population were correctly reconstructed by NJ and Bayesian methods receiving high bootstrap and posterior probability (PP) support, respectively. On the other hand, TreePuzzle failed to reconstruct or provide significant support for several clusters; high puzzling step support was associated with the inclusion of control sequences from the same geographic area as the target population. In contrary, all clusters were correctly reconstructed by hML as implemented in PhyML 3.0 receiving high bootstrap support. We report that under the conditions of our study, hML using PhyML, NJ and Bayesian methods were the most sensitive for the reconstruction of epidemiological links mostly from sexually infected individuals.
    Virus Research 03/2012; 166(1-2):54-60. DOI:10.1016/j.virusres.2012.03.002 · 2.32 Impact Factor
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    ABSTRACT: Phylogenetic and genetic analyses have proven a valuable tool to infer epidemiological links between human immunodeficiency virus type-1 (HIV-1) isolates. These methods were applied in the present report for studying the genetic relatedness of the viral strains involved in two episodes of suspected HIV-1 transmission. Provide any evidence that may help establish or refute the transmission link. In the first case, a leukemic patient became HIV-1 positive following the transfusion of platelets from a donor who was subsequently found to have tested false HIV-seronegative and to be sexual partner to an infected woman. In the second, a wife claimed to have acquired the infection from her husband who had concealed his infected status. The viral pairs detected in each of the suspected transmission cases exhibited common amino acid signatures and low genetic distances and segregated together in phylogenetic trees, thus showing a level of genetic relatedness similar to reference pairs known with certainty to be epidemiologically linked. These findings corroborated the existence of a direct transmission link in both the episodes with a high level of confidence.
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