19 Viruses have each caused more than 100 deaths/year, most are enveloped
Summary Table
| Virus | Envelope Status | Approximate Annual Deaths |
|---|---|---|
| Hepatitis B Virus | Enveloped | ~1,100,000 |
| Hepatitis C Virus | Enveloped | ~200,000 |
| HIV-1 | Enveloped | Hundreds of thousands |
| SARS-CoV-2 | Enveloped | Thousands monthly |
| Influenza viruses | Enveloped | Hundreds of thousands |
| Measles virus | Enveloped | ~95,000 (2024) |
| Dengue virus | Enveloped | 11,201 (2024) |
| Mpox virus | Enveloped | >1,788 (Africa 2024-2025) |
| RSV | Enveloped | Tens of thousands |
| HPV | Non-enveloped | Hundreds of thousands (cancers) |
| Hepatitis A Virus | Quasi-enveloped | >100 |
| Hepatitis E Virus | quasi-enveloped | Thousands |
| Rotavirus | Non-enveloped | Thousands |
| Varicella-Zoster Virus | Enveloped | >100 |
| Rabies virus | Enveloped | >55,000 |
| HTLV-1/2 | Enveloped | >100 |
| Chikungunya virus | Enveloped | 229 (2025) |
| Lassa virus | Enveloped | Hundreds |
| Ebola viruses | Enveloped | Variable (outbreak-dependent) |
| West Nile Virus | Enveloped | Variable |
| Japanese Encephalitis Virus | Enveloped | Variable |
1. Hepatitis B Virus (HBV) – ENVELOPED
Approximately 1.3 million annual deaths from viral hepatitis (mostly HBV and HCV), with ~83% from hepatitis B. HBV is an enveloped DNA virus with an icosahedral capsid; the viral envelope contains surface proteins (HBsAg). pubmed.ncbi.nlm.nih
2. Hepatitis C Virus (HCV) – ENVELOPED
Approximately 17% of the 1.3 million viral hepatitis deaths annually. HCV is a small (55–65 nm), enveloped, positive-sense single-stranded RNA virus with envelope glycoproteins E1 and E2 embedded in a lipid membrane. nature
3. Human Immunodeficiency Virus type 1 (HIV-1) – ENVELOPED
HIV causes hundreds of thousands of deaths annually worldwide. HIV-1 is an enveloped retrovirus; its envelope is formed by viral gp41 and gp120 envelope glycoproteins. pmc.ncbi.nlm.nih
4. SARS-CoV-2 (COVID-19 virus) – ENVELOPED
Still causing thousands of deaths monthly worldwide. SARS-CoV-2 is an enveloped coronavirus with spike (S), envelope (E), and membrane (M) proteins embedded in its lipid envelope. nature
5. Influenza viruses (types A, B, C, D) – ENVELOPED
Seasonal influenza causes hundreds of thousands of deaths annually. Influenza viruses are enveloped negative-sense RNA viruses with hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins. pubs.rsc
6. Measles virus – ENVELOPED
Approximately 95,000 deaths in 2024. Measles virus is an enveloped negative-strand RNA virus in the genus Morbillivirus, with fusion (F) and hemagglutinin (H) envelope glycoproteins. pmc.ncbi.nlm.nih
7. Dengue virus – ENVELOPED
11,201 deaths and over 14 million cases in 2024. Dengue virus is an enveloped flavivirus approximately 50 nm in diameter, with envelope (E) and membrane (M) proteins in its lipid envelope. nature
8. Mpox virus (Monkeypox virus) – ENVELOPED
Over 1,788 deaths in Africa alone between January 2024 and May 2025. Mpox virus is an enveloped double-stranded DNA virus of the Orthopoxvirus genus; its envelope contains proteins B6R, C19L, and A35R. pmc.ncbi.nlm.nih
9. Respiratory Syncytial Virus (RSV) – ENVELOPED
Tens of thousands of deaths annually, especially in infants and older adults. RSV is an enveloped virus with a negative-sense, single-stranded RNA genome (~15.2 kb); the envelope contains three viral transmembrane glycoproteins: G, F, and SH. pmc.ncbi.nlm.nih
10. Human Papillomavirus (HPV) – NON-ENVELOPED
Hundreds of thousands of deaths annually from HPV-associated cancers. HPV virions are icosahedral, non-enveloped, 52–55 nm in diameter, with a capsid composed of 72 pentameric capsomeres of L1 protein. pmc.ncbi.nlm.nih
11. Hepatitis A Virus (HAV) – QUASI-ENVELOPED (unique dual nature)
More than 100 deaths per year globally. HAV is unusual: classically non-enveloped when shed in feces (stable in the environment), but acquires a host-derived membrane envelope (quasi-envelope or eHAV) when circulating in blood within the liver, protecting it from neutralizing antibodies. nature
12. Hepatitis E Virus (HEV) – NON-ENVELOPED (with quasi-enveloped forms in blood)
Thousands of deaths per year, especially in pregnant women and outbreak settings. HEV structure is similar to HAV; typically non-enveloped but can acquire host membranes in blood (quasi-enveloped forms).
13. Rotavirus – NON-ENVELOPED
Many thousands of deaths annually in young children, especially where vaccine coverage is low. Rotaviruses are non-enveloped, triple-layered icosahedral particles (70 nm) with double-stranded RNA genome; virions consist of an inner core, middle capsid (VP6), and outer capsid (VP7 and VP4). pubmed.ncbi.nlm.nih
14. Varicella-Zoster Virus (VZV) – ENVELOPED
Modest but non-trivial annual global death burden from zoster complications in older and immunocompromised populations. VZV is an enveloped alphaherpesvirus; envelope glycoproteins include gE, gI, gB, gC, gH, and gL. pubmed.ncbi.nlm.nih
15. Rabies virus – ENVELOPED
Tens of thousands of deaths per year (WHO estimates >55,000 annually). Rabies virus is an enveloped rhabdovirus with a bullet-shaped morphology; the cell-derived lipid membrane envelope contains surface glycoprotein (G) trimers. nature
16. Human T-Lymphotropic Virus (HTLV-1/2) – ENVELOPED
Global mortality likely exceeds 100 per year from adult T-cell leukemia/lymphoma and myelopathy. HTLV-1 is an enveloped retrovirus with envelope glycoproteins (surface SU and transmembrane TM) derived from a precursor (gp62). pubmed.ncbi.nlm.nih
17. Chikungunya virus – ENVELOPED
229 deaths reported in 2025, with over 485,000 cases. Chikungunya is an enveloped alphavirus (family Togaviridae) with envelope glycoproteins E1 and E2. ecdc.europa
18. Lassa virus – ENVELOPED
Hundreds of deaths annually in West Africa. Lassa virus is an enveloped arenavirus with a single-stranded, bisegmented RNA genome; the envelope contains trimeric glycoprotein complex (GPC) spikes. nature
19. Ebola viruses (Zaire ebolavirus and others) – ENVELOPED
Death toll varies by year with outbreaks. Ebola virus is an enveloped filovirus (80 nm diameter, ~970 nm long); the viral envelope contains glycoprotein (GP) trimers. nature
20. Other arboviruses with fluctuating annual tolls
- West Nile Virus – ENVELOPED: Enveloped flavivirus (~50 nm) with envelope (E) and membrane (M) proteins journals.asm
- Japanese Encephalitis Virus – ENVELOPED: Enveloped flavivirus with envelope protein (E) consisting of three domains (DI, DII, DIII) pmc.ncbi.nlm.nih
Key Observations:
The vast majority of high-mortality viruses are enveloped (17 of 21 listed), reflecting the fact that enveloped viruses include many chronic bloodborne and respiratory pathogens.
Only three viruses are definitively non-enveloped: HPV, rotavirus, and hepatitis E virus (with quasi-enveloped forms).
Hepatitis A virus is unique as a "quasi-enveloped" virus—it exists in non-enveloped form in the environment (stable for fecal-oral transmission) but wraps itself in host-derived membranes within the liver to evade antibodies. unclineberger
Envelope status correlates with transmission and persistence strategies: Non-enveloped viruses (HPV, rotavirus) are environmentally stable and spread via fecal-oral or direct contact routes; enveloped viruses (HIV, hepatitis B/C, influenza, coronaviruses) often require respiratory droplets, blood, or direct mucosal contact but can evade immune responses more effectively through envelope glycoprotein variation.
This comprehensive annotation should help you understand the structural biology and epidemiological significance of these major viral pathogens.