Last data update: Jul 01, 2024. (Total: 47134 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Jayashankar L [original query] |
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Building the framework for standardized clinical laboratory reporting of next generation sequencing data for resistance-associated mutations in Mycobacterium tuberculosis complex.
Tornheim JA , Starks AM , Rodwell TC , Gardy JL , Walker TM , Cirillo DM , Jayashankar L , Miotto P , Zignol M , Schito M . Clin Infect Dis 2019 69 (9) 1631-1633 ![]() ![]() Tuberculosis is the primary infectious disease killer worldwide, with a growing threat from multidrug- resistant cases. Unfortunately, classic growth-based phenotypic drug susceptibility testing (DST) remains difficult, costly and time-consuming, while current rapid molecular testing options are limited by the diversity of antimicrobial resistant genotypes that can be detected at once. Next generation sequencing (NGS) offers the opportunity for rapid, comprehensive DST without the time or cost burden of phenotypic tests and can provide useful information for global surveillance. As access to NGS expands, it will be important to ensure that results are communicated clearly, are consistent, are comparable between laboratories, and are associated with clear guidance on clinical interpretation of results. This viewpoint summarizes two expert workshops regarding a standardized report format, focusing on relevant variables, terminology, and required minimal elements for clinical and laboratory reports with a proposed standardized template for clinical reporting of NGS results for Mycobacterium tuberculosis. |
Eliminating perinatal HIV in the United States: mission possible
Gnanashanmugam D , Rakhmanina N , Crawford K , Nesheim S , Ruel T , Birkhead GS , Chakraborty R , Lawrence R , Jean-Philippe P , Jayashankar L , Hoover A , Statton A , D'Souza P , Fitzgibbon J , Hazra R , Warren B , Smith S , Abrams EJ . AIDS 2018 33 (3) 377-385 In 2015, only 53 infants born in the United States acquired HIV, the lowest recorded number of perinatal HIV infections. Recognizing this significant achievement, we must acknowledge that the United States has not yet reached the goal of eliminating perinatal HIV transmission. This manuscript describes different approaches to perinatal HIV preventive services among five states and the District of Columbia as case studies. Continuous focus on improving identification, surveillance and prevention of HIV infection in pregnant women and their infants is necessary to reach the goal of eliminating perinatal HIV transmission in the United States. |
Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal
Van Rompay KK , Trott KA , Jayashankar K , Geng Y , Labranche CC , Johnson JA , Landucci G , Lipscomb J , Tarara RP , Canfield DR , Heneine W , Forthal DN , Montefiori D , Abel K . Retrovirology 2012 9 57 ![]() BACKGROUND: We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus replication for years. Transient CD8+ cell depletion or short-term tenofovir interruption within 1 to 5 years of treatment demonstrated that a combination of CD8+ cell-mediated immune responses and continued tenofovir therapy was required for sustained suppression of viremia. We report here follow-up data on 5 such animals that received tenofovir for 8 to 14 years. RESULTS: Although one animal had a gradual increase in viremia from 3 years onwards, the other 4 tenofovir-treated animals maintained undetectable viremia with occasional viral blips (≤ 300 RNA copies/ml plasma). When tenofovir was withdrawn after 8 to 10 years from three animals with undetectable viremia, the pattern of occasional episodes of low viremia (≤ 3600 RNA/ml plasma) continued throughout the 10-month follow-up period. These animals had low virus levels in lymphoid tissues, and evidence of multiple SIV-specific immune responses. CONCLUSION: Under certain conditions (i.e., prolonged antiviral therapy initiated early after infection; viral mutants with reduced drug susceptibility) a virus-host balance characterized by strong immunologic control of virus replication can be achieved. Although further research is needed to translate these findings into clinical applications, these observations provide hope for a functional cure of HIV infection via immunotherapeutic strategies that boost antiviral immunity and reduce the need for continuous antiretroviral therapy. |
Compared to subcutaneous tenofovir, oral tenofovir disoproxyl fumarate administration preferentially concentrates the drug into gut-associated lymphoid cells in simian immunodeficiency virus-infected macaques
Van Rompay KK , Babusis D , Abbott Z , Geng Y , Jayashankar K , Johnson JA , Lipscomb J , Heneine W , Abel K , Ray AS . Antimicrob Agents Chemother 2012 56 (9) 4980-4 To compare tissue-based pharmacokinetics and efficacy of oral tenofovir disoproxyl fumarate (TDF) versus subcutaneous tenofovir (TFV), macaques were treated for 2 weeks starting 1 week after simian immunodeficiency virus inoculation. Despite lower plasma TFV levels in the oral TDF arm, similar TFV diphosphate levels and antiviral activities were measured in lymphoid cells of most tissues. In intestinal tissues, however, oral TDF resulted in higher active drug levels, associated with lower virus levels and better immune preservation. |
5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication
Ranjan P , Jayashankar L , Deyde V , Zeng H , Davis WG , Pearce MB , Bowzard JB , Hoelscher MA , Jeisy-Scott V , Wiens ME , Gangappa S , Gubareva L , Garcia-Sastre A , Katz JM , Tumpey TM , Fujita T , Sambhara S . Virol J 2010 7 (1) 102 ![]() BACKGROUND: Emergence of drug-resistant strains of influenza viruses, including avian H5N1 with pandemic potential, 1918 and 2009 A/H1N1 pandemic viruses to currently used antiviral agents, neuraminidase inhibitors and M2 Ion channel blockers, underscores the importance of developing novel antiviral strategies. Activation of innate immune pathogen sensor Retinoic Acid Inducible Gene-I (RIG-I) has recently been shown to induce antiviral state. RESULTS: In the present investigation, using real time RT-PCR, immunofluorescence, immunoblot, and plaque assay we show that 5'PPP-containing single stranded RNA (5PPP-RNA), a ligand for the intracytoplasmic RNA sensor, RIG-I can be used as a prophylactic agent against known drug-resistant avian H5N1 and pandemic influenza viruses. 5'PPP-RNA treatment of human lung epithelial cells inhibited replication of drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza viruses in a RIG-I and type 1 interferon dependant manner. Additionally, 5'PPP-RNA treatment also inhibited 2009 H1N1 viral replication in vivo in mice. CONCLUSIONS: Our findings suggest that 5PPP-RNA mediated activation of RIG-I can suppress replication of influenza viruses irrespective of their genetic make-up, pathogenicity, and drug-sensitivity status. |
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