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Towards Understanding Long COVID: SARS-CoV-2 Strikes the Host Cell Nucleus
1Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Ministerio de Educación y Cultura, Montevideo 11600, Uruguay.
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) impacts multiple body systems and can affect the host cell nucleus. Viral components entering the nucleus may lead to genomic integration and chronic inflammation.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has demonstrated widespread effects beyond acute respiratory illness, including long-term sequelae (Long COVID) and multi-systemic involvement.
- Current understanding of SARS-CoV-2 replication traditionally focused on cytoplasmic processes, largely excluding nuclear interactions.
Purpose of the Study:
- To investigate the extent to which SARS-CoV-2 components interact with and potentially alter the host cell nucleus.
- To explore the implications of nuclear viral presence, including potential genomic integration and its consequences.
Main Methods:
- Analysis of cumulative evidence on SARS-CoV-2 protein and RNA localization within host cells.
- Review of studies examining nuclear pore transport disruption by viral proteins.
- Examination of research on SARS-CoV-2 sequence retrotranscription and integration into the host genome.
Main Results:
- Multiple SARS-CoV-2 proteins (Spike, Nucleocapsid, Nsp1, Nsp3, ORF3d, ORF6, ORF9a) and some viral RNA can enter the host cell nucleus via nuclear localization signals or protein shuttling.
- Evidence suggests SARS-CoV-2 sequences can be retrotranscribed and integrated into the host genome, forming chimeric genes.
- Expression of these chimeric proteins may lead to neo-antigen formation, autoimmunity, and chronic inflammation.
Conclusions:
- SARS-CoV-2 actively invades the host cell nucleus, challenging previous models of viral lytic cycles.
- Nuclear integration of viral genetic material presents a potential mechanism for persistent viral effects, chronic inflammation, and autoimmune responses post-infection.
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