Six categories. Every microbe that touches human biology.
The same systematic approach for each — structure, mechanism of harm, immune signature, mutation pressure. The scale ladder, viewed from the other side of the encounter.
Viruses
Influenza, coronaviruses, HIV, herpes, ebola — fast mutation; highest-priority threat class.
Bacteria
TB, staph, strep, mycobacteria — antibiotic resistance and cell-cell warfare with the immune system.
Fungi
Candida, aspergillus, cryptococcus — emerging threats with few available drug classes.
Parasites
Plasmodium, helminths, trypanosomes — global disease burden; complex life cycles.
Prions
CJD, kuru — misfolded protein aggregates that stress-test every assumption in the model.
Microbiome
Gut, skin, respiratory commensals — not every microbe is a threat; many are partners.
Viruses
The fastest-evolving category. Viruses hijack host cellular machinery and mutate at rates that outpace immune memory — making them the highest-priority target for the human model. Two entries currently filled, both cardiovascular.
Coxsackievirus B
Non-enveloped positive-sense single-stranded RNA enterovirus with six serotypes (B1–B6). The leading infectious cause of acute myocarditis in the developed world and a major antecedent of dilated cardiomyopathy. Enters cardiomyocytes via the coxsackievirus-adenovirus receptor (CAR) concentrated at intercalated discs; destroys them by direct cytolysis and protease 2A-mediated cleavage of dystrophin.
Structure
| Capsid | T=1 icosahedral, 60 protomers; VP1, VP2, VP3 (surface), VP4 (internal, stabilising) |
| Genome | ~7.4 kb +ssRNA; single ORF flanked by 5′/3′ UTRs; VPg protein at 5′ end; IRES-driven, cap-independent translation |
| Entry receptor | CAR (Coxsackievirus-Adenovirus Receptor) — concentrated at cardiac intercalated discs; CD55 (decay-accelerating factor) acts as attachment co-receptor |
| Stability | Stable at low pH (gut transit); thermolabile above 50 °C; transmitted fecal-oral and respiratory |
| Serotypes | B1–B6; B3 and B5 most commonly linked to myocarditis; B4 associated with pancreatitis |
Mechanisms of Harm
Direct cytolytic replication
CVB enters cardiomyocytes via CAR at intercalated discs — the same junctions mediating electrical coupling — facilitating spread across the myocardial syncytium. Viral protease 3Cpro and RdRp (3Dpol) drive replication in membrane-associated complexes. Progeny virions accumulate until lytic release destroys the cell.
Protease 2A cleavage of dystrophin
Viral protease 2Apro cleaves human dystrophin at the hinge-3 domain, severing the cytoskeleton–sarcolemma link. This increases Ca²⁺ sarcolemmal permeability, initiates a necrotic cascade independent of cytolysis, and creates a phenotype mechanistically similar to Duchenne muscular dystrophy — explaining why DCM can persist long after viral clearance.
Immune-mediated injury & autoimmunity
CD8⁺ cytotoxic T lymphocytes target infected cardiomyocytes in the adaptive phase. Molecular mimicry between CVB VP1 capsid proteins and cardiac myosin heavy chain (MHC-α, MHC-β) generates autoreactive T cells and anti-cardiac myosin antibodies that continue damaging the myocardium after viral clearance — the autoimmune mechanism of post-viral DCM (~30% of severe cases).
Cardiac Pathology
| Phase | Mechanism | Tissue signature |
|---|---|---|
| Acute (days 1–14) | Direct cytolysis, innate inflammation | Cardiomyocyte necrosis, neutrophil/macrophage infiltrate, oedema |
| Subacute (weeks 2–8) | CD8⁺ T-cell cytotoxicity, immune-complex deposition | Lymphocytic infiltrate (Dallas criteria), ongoing myocyte death |
| Chronic / healed | Scar formation or ongoing autoimmune activation | Interstitial fibrosis, ventricular remodelling, chamber dilation — DCM in ~30% of severe cases |
Immune Signature
Cross-Atlas Connections
References
- Cooper LT Jr. Myocarditis. N Engl J Med. 2009;360(15):1526–38. doi:10.1056/NEJMra0800028 · PubMed 19357408
- Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis. J Am Coll Cardiol. 2012;59(9):779–92. doi:10.1016/j.jacc.2011.09.074 · PubMed 22361396
- Rose NR. Viral myocarditis. Curr Opin Rheumatol. 2016;28(4):383–9. doi:10.1097/BOR.0000000000000303 · PubMed 27166925
- Yang D, et al. Coxsackievirus B3 replication, apoptosis, and persistence in the heart. Cell Microbiol. 2009;11(11):1658–71. doi:10.1111/j.1462-5822.2009.01359.x · PubMed 19575749
- NCBI Taxonomy — Enterovirus B, species; Coxsackievirus B1–B6, serotypes. ncbi.nlm.nih.gov/Taxonomy
SARS-CoV-2 (cardiac effects)
Betacoronavirus responsible for COVID-19. This entry focuses on cardiac interactions: ACE2-dependent entry into cardiomyocytes, direct viral myocarditis, cytokine-storm-mediated myocardial injury, microvascular thrombosis and endotheliopathy, arrhythmias, and right ventricular failure. ACE2 — the primary receptor — is expressed on cardiomyocytes, endothelial cells, and pericytes, making the heart directly accessible to the virus.
Structure — Key Cardiac-Relevant Proteins
| Spike (S) | Binds ACE2 (S1 domain); mediates membrane fusion (S2); primed by TMPRSS2. ACE2 is expressed on cardiomyocytes, endothelial cells, and pericytes — the molecular basis for cardiac tropism. |
| NSP12 (RdRp) | Genome replication polymerase; target of remdesivir. |
| M (membrane) | Structural; suppresses IFN-β induction — key immune evasion mechanism during early infection. |
| N (nucleocapsid) | RNA packaging and replication complex scaffold; primary diagnostic antigen. |
| Genome | ~30 kb +ssRNA; largest RNA viral genome; 16 non-structural proteins (NSP1–16) plus 4 structural (S, E, M, N). |
Mechanisms of Cardiac Injury
1 · Direct viral myocarditis
SARS-CoV-2 spike binds ACE2 on cardiomyocytes. Direct infection confirmed in autopsy specimens by in situ hybridisation for viral RNA and electron microscopy. Causes both viral cytolysis and immune-cell-mediated myocyte killing, paralleling CVB myocarditis. Clinical presentation ranges from asymptomatic troponin rise to fulminant myocarditis.
2 · ACE2 downregulation → RAAS imbalance
Spike binding internalises ACE2, reducing surface expression and shifting local RAAS toward excess angiotensin II (vasoconstrictive, pro-inflammatory, pro-fibrotic). This promotes cardiomyocyte inflammation, oxidative stress, and fibrosis independent of direct viral replication.
3 · Cytokine storm (immune-mediated injury)
Severe COVID-19 triggers systemic hyperinflammation: markedly elevated IL-6, IL-1β, TNF-α, and ferritin. Myocardial inflammation in this context is partly a bystander effect of systemic cytokines — macrophage activation syndrome (MAS)-like phenotypes described in fatal cases with prominent cardiac involvement.
4 · Endotheliopathy and microvascular thrombosis
SARS-CoV-2 activates endothelium; elevates D-dimer, fibrinogen, and von Willebrand factor; induces platelet hyperactivation. Creates conditions for: coronary microvascular thrombosis (type 2 MI), acute plaque rupture (type 1 MI in patients with pre-existing atherosclerosis), and pulmonary embolism leading to right ventricular pressure overload.
5 · Arrhythmias
QTc prolongation, atrial fibrillation, and ventricular arrhythmias common in hospitalised patients. Mechanisms: myocardial inflammation disrupts conduction; electrolyte derangements; hypoxia; catecholamine surge; direct viral effects on ion-channel expression (including Nav1.5, hERG).
Cardiac Pathology — Frequency in Hospitalised Patients
| Syndrome | Frequency | Primary mechanism |
|---|---|---|
| Troponin elevation (asymptomatic) | 20–30% | Demand ischaemia, microvascular injury, subclinical myocarditis |
| Acute myocarditis (clinical) | 1–5% | Direct viral + immune-mediated |
| Type 1 MI | ~2–4% | Plaque rupture in inflammatory context |
| Type 2 MI | ~5–10% | Demand-supply mismatch, microvascular thrombosis |
| Arrhythmia (any) | 5–20% | Multi-factorial (see above) |
| Right ventricular failure | Uncommon; high mortality | Pulmonary hypertension, PE, high-PEEP ventilation |
Immune Signature
Cross-Atlas Connections
References
- Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2. Cell. 2020;181(2):271–280. doi:10.1016/j.cell.2020.02.052 · PubMed 32142651
- Lindner D, Fitzek A, Brauninger H, et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol. 2020;5(11):1281–5. doi:10.1001/jamacardio.2020.3551 · PubMed 32730555
- Giustino G, Croft LB, Stefanini GG, et al. Characterization of myocardial injury in patients with COVID-19. J Am Coll Cardiol. 2020;76(18):2043–55. doi:10.1016/j.jacc.2020.08.069 · PubMed 33121713
- Eiros R, Barreiro-Perez M, Martin-Garcia A, et al. Pericarditis and myocarditis long after SARS-CoV-2 infection. medRxiv. 2020. doi:10.1101/2020.07.12.20151316
Viruses — Additional Entries
Bacteria
Fungi
Parasites
Prions
Protein-only infectious agents — no nucleic acid genome. PrPSc misfolding nucleates conversion of normal PrPC, producing uniformly fatal transmissible spongiform encephalopathies. CJD, kuru, fatal familial insomnia — edge cases that stress-test every assumption about what constitutes an infectious agent.
Human Microbiome
Help expand the Pathogen Atlas
Every entry follows the same schema: structured frontmatter, peer-reviewed citations, and cross-atlas links to the host biology and medicine atlases.