Systemic viral spreading and defective host responses are associated with fatal Lassa fever in macaques

Baillet, Nicolas; Reynard, Stéphanie; Perthame, Émeline; Hortion, Jimmy; Journeaux, Alexandra; Mateo, Mathieu; Carnec, Xavier; Schaeffer, Justine; Picard, Caroline; Barrot, Laura; Barron, Stéphane; Vallvé, Audrey; Duthey, Aurélie; Jacquot, Frédéric; Boehringer, Cathy; Jouvion, Grégory; Pietrosemoli, Natalia; Legendre, Rachel; Dillies, Marie‐Agnès; Allan, Richard; Legras-Lachuer, Catherine; Carbonnelle, Caroline; Raoul, Hervé; Baize, Sylvain

doi:10.1038/s42003-020-01543-7

Cited by 21 publications

(34 citation statements)

References 80 publications

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“…Neutralizing antibodies, if at all, only appear several months post-infection [37]. Similar observations were made with non-human primates, which develop no or only low levels of neutralizing antibodies after LASV infection [38,39]. Furthermore, experiments with plasma transfer from LASV survivors in non-human primates and humans show variable outcomes, and protection was only achieved in some cases [40][41][42].…”

Section: Discussionsupporting

confidence: 58%

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Experimental Morogoro Virus Infection in Its Natural Host, Mastomys natalensis

Hoffmann

Wurr

Pallasch

et al. 2021

Viruses

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Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely Mastomys natalensis (M. natalensis). In this study, we investigated the history of infection and virus transmission within the natural host population. To this end, we infected M. natalensis at different ages with MORV and measured the health status of the animals, virus load in blood and organs, the development of virus-specific antibodies, and the ability of the infected individuals to transmit the virus. To explore the impact of the lack of evolutionary virus–host adaptation, experiments were also conducted with Mobala virus (MOBV), which does not share M. natalensis as a natural host. Animals infected with MORV up to two weeks after birth developed persistent infection, seroconverted and were able to transmit the virus horizontally. Animals older than two weeks at the time of infection rapidly cleared the virus. In contrast, MOBV-infected neonates neither developed persistent infection nor were able to transmit the virus. In conclusion, we demonstrate that MORV is able to develop persistent infection in its natural host, but only after inoculation shortly after birth. A related arenavirus that is not evolutionarily adapted to M. natalensis is not able to establish persistent infection. Persistently infected animals appear to be important to maintain virus transmission within the host population.

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Section: Discussionsupporting

confidence: 58%

“…T cells have already been shown to be important for LASV, MORV, and MOBV clearance in experimentally infected interferon-alpha/beta receptor-deficient mice [28]. Moreover, they also play a crucial role in the disease progression and outcome of LASV infections in humans and non-human primates [38,39,49,50].…”

Section: Discussionmentioning

confidence: 99%

Experimental Morogoro Virus Infection in Its Natural Host, Mastomys natalensis

Hoffmann

Wurr

Pallasch

et al. 2021

Viruses

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“…A noticeable sub-group of CD3-low T-lymphocytes appeared in which HERV-W ENV protein was predominantly expressed, whereas it remained minimal and HERV-W negative in control cultures not exposed to the virus. These observations may corroborate previous works describing superantigen motifs of SARS-CoV-2 spike protein 43 , and may involve cellular mechanisms associated to lymphopenia and hyperin ammation already characterized for other emerging viruses (e.g., Ebola or Lassa) 48,49 . However, because HERV-W ENV was also shown to display superantigen-like effect 28 , the origin of this effect on T-lymphocytes or potentially combined effects are questioned.…”

Section: Discussionsupporting

confidence: 91%

SARS-CoV-2 induces transcription of human endogenous retrovirus RNA followed by type W envelope protein expression in human lymphoid cells.

Charvet¹,

Mazelier

Brunel³

et al. 2021

Preprint

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Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after resolution of the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. We demonstrate here that an initial exposure to SARS-CoV-2 virus activates early HERV-W and K transcription in peripheral blood mononuclear cell (PBMC) cultures from healthy donors. Within a week of primary PBMC culture, only HERV-W ENV protein expression was detected in lymphoid cells of some donors, although SARS-CoV-2 infection of PBMC was not observed. HERV activation was reproduced with UV-inactivated virus and with a recombinant spike protein. Interestingly, exposure to SARS-CoV-2 protein induced a significant production of interleukin 6 in PBMC, independently from detectable HERV expression. Altogether, these results show that SARS-CoV-2 viral protein could induce HERV-W ENV expression in lymphocytes from some individuals, underlying the importance to further address the implicated molecular pathways, to understand patients‘ genetic susceptibility associated to the activation of HERV-W and its possible relevance for targeting therapeutic intervention in COVID-19 associated syndromes.

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“…In previously described [72]. Alternatively, in COVID-19 patients, our observations may corroborate previous reports describing superantigen motifs of SARS-CoV-2 spike protein [73], and may involve cellular mechanisms associated to lymphopenia and hyperinflammation as already characterized for other emerging viruses (e.g., Ebola or Lassa) [78,79]. However, because HERV-W ENV has also been shown to display superantigen-like effect [51], the origin of this short-term effect on T-lymphocytes may be questioned.…”

Section: Discussionsupporting

confidence: 90%

SARS-CoV-2 induces human endogenous retrovirus type W envelope protein expression in blood lymphocytes and in tissues of COVID-19 patients

Charvet¹,

Brunel²,

Pierquin³

et al. 2022

Preprint

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Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes.

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Systemic viral spreading and defective host responses are associated with fatal Lassa fever in macaques

Cited by 21 publications

References 80 publications

Experimental Morogoro Virus Infection in Its Natural Host, Mastomys natalensis

Experimental Morogoro Virus Infection in Its Natural Host, Mastomys natalensis

SARS-CoV-2 induces transcription of human endogenous retrovirus RNA followed by type W envelope protein expression in human lymphoid cells.

SARS-CoV-2 induces human endogenous retrovirus type W envelope protein expression in blood lymphocytes and in tissues of COVID-19 patients

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