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  1. AU="Sandile Cele"
  2. AU=Benzinger Tammie L S
  3. AU="Fallah, Nader Nader"

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  1. Artikel ; Online: A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy.

    Allison J Greaney / Tyler N Starr / Rachel T Eguia / Andrea N Loes / Khadija Khan / Farina Karim / Sandile Cele / John E Bowen / Jennifer K Logue / Davide Corti / David Veesler / Helen Y Chu / Alex Sigal / Jesse D Bloom

    PLoS Pathogens, Vol 18, Iss 2, p e

    2022  Band 1010248

    Abstract: Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral ... ...

    Abstract Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the "class 3" epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2022-02-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.

    Gila Lustig / Sandile Cele / Farina Karim / Anne Derache / Abigail Ngoepe / Khadija Khan / Bernadett I Gosnell / Mahomed-Yunus S Moosa / Ntombi Ntshuba / Suzaan Marais / Prakash M Jeena / Katya Govender / John Adamson / Henrik Kløverpris / Ravindra K Gupta / Rohen Harrichandparsad / Vinod B Patel / Alex Sigal

    PLoS Pathogens, Vol 17, Iss 9, p e

    2021  Band 1009871

    Abstract: HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are ... ...

    Abstract HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2021-09-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

    Khadija Khan / Farina Karim / Yashica Ganga / Mallory Bernstein / Zesuliwe Jule / Kajal Reedoy / Sandile Cele / Gila Lustig / Daniel Amoako / Nicole Wolter / Natasha Samsunder / Aida Sivro / James Emmanuel San / Jennifer Giandhari / Houriiyah Tegally / Sureshnee Pillay / Yeshnee Naidoo / Matilda Mazibuko / Yoliswa Miya /
    Nokuthula Ngcobo / Nithendra Manickchund / Nombulelo Magula / Quarraisha Abdool Karim / Anne von Gottberg / Salim S. Abdool Karim / Willem Hanekom / Bernadett I. Gosnell / COMMIT-KZN Team / Richard J. Lessells / Tulio de Oliveira / Mahomed-Yunus S. Moosa / Alex Sigal

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Band 7

    Abstract: Emerging SARS-CoV-2 Omicron sub-lineages BA.4 and BA.5 raise concerns about potential immune evasion. Here, Khan et al. show that both BA.4 and BA.5 are able to escape immune response induced by prior BA.1 infection, but that this effect is less ... ...

    Abstract Emerging SARS-CoV-2 Omicron sub-lineages BA.4 and BA.5 raise concerns about potential immune evasion. Here, Khan et al. show that both BA.4 and BA.5 are able to escape immune response induced by prior BA.1 infection, but that this effect is less pronounced in vaccinated individuals.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-08-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

    Laurelle Jackson / Jessica Hunter / Sandile Cele / Isabella Markham Ferreira / Andrew C Young / Farina Karim / Rajhmun Madansein / Kaylesh J Dullabh / Chih-Yuan Chen / Noel J Buckels / Yashica Ganga / Khadija Khan / Mikael Boulle / Gila Lustig / Richard A Neher / Alex Sigal

    eLife, Vol

    2018  Band 7

    Abstract: HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If ... ...

    Abstract HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.
    Schlagwörter HIV induced cell death ; cell-to-cell spread ; Lymph node ; viral fitness ; multiple Infections per cell ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2018-03-01T00:00:00Z
    Verlag eLife Sciences Publications Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: HIV status alters disease severity and immune cell responses in Beta variant SARS-CoV-2 infection wave

    Farina Karim / Inbal Gazy / Sandile Cele / Yenzekile Zungu / Robert Krause / Mallory Bernstein / Khadija Khan / Yashica Ganga / Hylton Rodel / Ntombifuthi Mthabela / Matilda Mazibuko / Daniel Muema / Dirhona Ramjit / Thumbi Ndung'u / Willem Hanekom / Bernadett Gosnell / COMMIT-KZN Team / Richard J Lessells / Emily B Wong /
    Tulio de Oliveira / Mahomed-Yunus S Moosa / Gil Lustig / Alasdair Leslie / Henrik Kløverpris / Alex Sigal

    eLife, Vol

    2021  Band 10

    Abstract: There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), ... ...

    Abstract There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.
    Schlagwörter SARS-CoV-2 ; COVID-19 ; HIV ; antiretroviral therapy ; beta variant ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2021-10-01T00:00:00Z
    Verlag eLife Sciences Publications Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage

    Cathrine Scheepers / Josie Everatt / Daniel G. Amoako / Houriiyah Tegally / Constantinos Kurt Wibmer / Anele Mnguni / Arshad Ismail / Boitshoko Mahlangu / Bronwen E. Lambson / Darren P. Martin / Eduan Wilkinson / James Emmanuel San / Jennifer Giandhari / Nelia Manamela / Noxolo Ntuli / Prudence Kgagudi / Sandile Cele / Simone I. Richardson / Sureshnee Pillay /
    Thabo Mohale / Upasana Ramphal / Yeshnee Naidoo / Zamantungwa T. Khumalo / Gaurav Kwatra / Glenda Gray / Linda-Gail Bekker / Shabir A. Madhi / Vicky Baillie / Wesley C. Van Voorhis / Florette K. Treurnicht / Marietjie Venter / Koleka Mlisana / Nicole Wolter / Alex Sigal / Carolyn Williamson / Nei-yuan Hsiao / Nokukhanya Msomi / Tongai Maponga / Wolfgang Preiser / Zinhle Makatini / Richard Lessells / Penny L. Moore / Tulio de Oliveira / Anne von Gottberg / Jinal N. Bhiman

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Band 9

    Abstract: The SARS-CoV-2 PANGO lineage C.1.2 has been under monitoring by global health authorities as it has spread worldwide. Here, Bhiman and colleagues characterise the emergence of the lineage, and its neutralisation sensitivity using data from vaccinees and ... ...

    Abstract The SARS-CoV-2 PANGO lineage C.1.2 has been under monitoring by global health authorities as it has spread worldwide. Here, Bhiman and colleagues characterise the emergence of the lineage, and its neutralisation sensitivity using data from vaccinees and previously infected individuals.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-04-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection

    Karim, Farina / Moosa, Mohamed YS / Gosnell, Bernadett / Sandile, Cele / Giandhari, Jennifer / Pillay, Sureshnee / Tegally, Houriiyah / Wilkinson, Eduan / San, Emmanuel James / Msomi, Nokukhanya / Mlisana, Koleka / Khan, Khadija / Bernstein, Mallory / Manickchund Nithendra, Nithendra / Singh, Lavanya / Ramphal, Upasana / Hanekom, Willem / Lessells, Richard J / Sigal, Alex /
    de Oliveira, Tulio

    medRxiv

    Abstract: While most people effectively clear SARS-CoV-2, there are several reports of prolonged infection in immunosuppressed individuals. Here we present a case of prolonged infection of greater than 6 months with the shedding of high titter SARS-CoV-2 in an ... ...

    Abstract While most people effectively clear SARS-CoV-2, there are several reports of prolonged infection in immunosuppressed individuals. Here we present a case of prolonged infection of greater than 6 months with the shedding of high titter SARS-CoV-2 in an individual with advanced HIV and antiretroviral treatment failure. Through whole-genome sequencing at multiple time points, we demonstrate the early emergence of the E484K substitution associated with escape from neutralizing antibodies, followed by other escape mutations and the N501Y substitution found in most variants of concern. This provides support to the hypothesis of intra-host evolution as one mechanism for the emergence of SARS-CoV-2 variants with immune evasion properties.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2021-06-04
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2021.06.03.21258228
    Datenquelle COVID19

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