Aleutian Disease of Mink: A Model for Persistent Infection

ABSTRACT Human coronaviruses (HuCV) are recognized respiratory pathogens. Data accumulated by different laboratories suggest their neurotropic potential. For example, primary cultures of human astrocytes and microglia were shown to be susceptible to an infection by the OC43 strain of HuCV (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800–806, 1997). We speculate that the neurotropism of HuCV will lead to persistence within the central nervous system, as was observed for murine coronaviruses. As a first step in the verification of our hypothesis, we have characterized the susceptibility of various human neural cell lines to infection by HuCV-OC43. Viral antigen, infectious virus progeny, and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, oligodendrocytic MO3.13, and the CHME-5 immortalized fetal microglial cell lines, were all susceptible to an acute infection by HuCV-OC43. Viral antigen and RNA and release of infectious virions were observed during persistent HuCV-OC43 infections (∼130 days of culture) of U-87 MG, U-373 MG, MO3.13, and H4 cell lines. Nucleotide sequences of RNA encoding the putatively hypervariable viral S1 gene fragment obtained after 130 days of culture were compared to that of initial virus input. Point mutations leading to amino acid changes were observed in all persistently infected cell lines. Moreover, an in-frame deletion was also observed in persistently infected H4 cells. Some point mutations were observed in some molecular clones but not all, suggesting evolution of the viral population and the emergence of viral quasispecies during persistent infection of H4, U-87 MG, and MO3.13 cell lines. These results are consistent with the potential persistence of HuCV-OC43 in cells of the human nervous system, accompanied by the production of infectious virions and molecular variation of viral genomic RNA.

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Absence of a robust innate immune response in rat neurons facilitates persistent infection of Borna disease virus in neuronal tissue

Cellular and Molecular Life Sciences ◽

10.1007/s00018-013-1402-5 ◽

2013 ◽

Vol 70 (22) ◽

pp. 4399-4410 ◽

Cited By ~ 9

Author(s):

Chia-Ching Lin ◽

Yuan-Ju Wu ◽

Bernd Heimrich ◽

Martin Schwemmle

Keyword(s):

Immune Response ◽

Disease Virus ◽

Innate Immune Response ◽

Persistent Infection ◽

Innate Immune ◽

Borna Disease Virus ◽

Neuronal Tissue ◽

Borna Disease

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COVID-19 re-infection or persistent infection in patient with acute myeloid leukaemia M3: a mini review

New Microbes and New Infections ◽

10.1016/j.nmni.2020.100830 ◽

2021 ◽

Vol 39 ◽

pp. 100830

Author(s):

H.A. Tehrani ◽

M. Darnahal ◽

S.A. Nadji ◽

S. Haghighi

Keyword(s):

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Persistent Infection ◽

Acute Myeloid

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SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

Clinical Infectious Diseases ◽

10.1093/cid/ciab380 ◽

2021 ◽

Author(s):

Manish C Choudhary ◽

Charles R Crain ◽

Xueting Qiu ◽

William Hanage ◽

Jonathan Z Li

Keyword(s):

Persistent Infection ◽

Viral Evolution ◽

Phylogenetic Reconstruction ◽

Geographic Region ◽

Antibody Treatment ◽

Viral Genomes ◽

Monoclonal Antibody Treatment ◽

Viral Sequences ◽

Sequence Characteristics ◽

Baseline Health

Abstract Background Both SARS-CoV-2 reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results Twenty reinfection and nine persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

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