Demystifying the Baltimore Classification System for SARS-CoV-2

February 21, 2024

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As the COVID-19 pandemic brought the novel SARS-CoV-2 virus to the forefront, scientists raced to characterize this previously unknown pathogen. An essential early step was assigning taxonomic classification – evaluating similarities to other viruses to guide research. The long-established system for viral taxonomy is the Baltimore classification scheme.

Introduced in 1971 by renowned virologist David Baltimore, this system groups viruses into seven classes designated by Roman numerals based on their genetic material and replication strategy. Familiarizing ourselves with these taxonomic groupings provides context on coronaviruses like SARS-CoV-2.

Baltimore 101: The Seven Virus Groups

The Baltimore system categorizes viruses into the following classes:

GroupGenetic MaterialExample Viruses
IDouble-stranded DNA (dsDNA)Adenoviruses, Herpesviruses
IISingle-stranded DNA (ssDNA)Parvoviruses
IIIDouble-stranded RNA (dsRNA)Reoviruses
IVPositive-sense single-stranded RNA (+ssRNA)Coronaviruses, Picornaviruses
VNegative-sense single-stranded RNA (-ssRNA)Orthomyxoviruses, Rhabdoviruses
VIPositive-sense single-stranded RNA (+ssRNA) with DNA intermediateRetroviruses
VIIDouble-stranded DNA (dsDNA) with RNA intermediateHepadnaviruses

DNA viruses utilize host replication machinery, while RNA viruses encode their own RNA polymerases. Additional nuances distinguish the groups based on precise transcription mechanisms.

Notably, SARS-CoV-2 falls under group IV – characterized by a +ssRNA genome that directly serves as messenger RNA.

Exploring the traits of this group sheds light on coronaviruses and their rapid emergence.

Positive-Sense ssRNA Viruses (Group IV)

Group IV or positive-sense RNA viruses have genomes that can be directly translated into viral proteins upon infection. This confers evolutionary advantages:

  • Rapid replication – No DNA/RNA replication needed to produce mRNA
  • High mutation rates – Error-prone viral RNA polymerases
  • Recombination potential – Co-infecting strains can mix +RNAs

These properties lead to great genetic diversity that enables Group IV viruses to quickly adapt to new hosts and environments.

However, there are also drawbacks:

  • Frequent mutations lead to defective interfering particles
  • No DNA phase – limited options for genetic repair

Understanding these evolutionary trade-offs provides insights into the zoonotic emergence of coronaviruses like SARS-CoV-2.


Baltimore Class IV: Coronaviruses & SARS-CoV-2

Coronaviruses belong to the order Nidovirales and possess the largest known positive-sense RNA genomes at 26-32 kilobases in length.

The subfamily Orthocoronavirinae contains the seven coronavirus genera – four common human coronaviruses and three zoonotic introductions:

  • SARS-CoV-2 – emerged in 2019, causes COVID-19
  • SARS-CoV – 2002-2004 SARS epidemic
  • MERS-CoV – sporadic outbreaks since 2012

The direct mRNA properties of Baltimore class IV likely facilitated rapid adaption in these host jumps from animal reservoirs.

High mutation rates also continually shape SARS-CoV-2 evolution, with Omicron markedly distinct from the original Wuhan strain. Understanding this diversity again relates back to the ssRNA classification.


Frequently Asked Questions

What were the key innovations of the Baltimore classification system?

The system grouped viruses by molecular biology properties (genome type, replication strategy) rather than just morphology. This reflected growing understanding of genetics. The seven groups remain robust 50 years later.

Could SARS-CoV-2 theoretically change Baltimore classifications?

No, the core features of its positive-sense RNA genome won’t change. Mutation could alter replication details that distinguish it from other coronaviruses, but SARS-CoV-2 fundamentally remains a group IV virus.

Why were positive-sense ssRNA viruses classified separately from negative-sense ssRNA viruses?

The mRNA properties of the +ssRNA genome provide immediate translational advantages. Meanwhile -ssRNA viruses require genome replication and transcription to mRNA. These differences drive divergent infection dynamics.

What other virus families belong to Baltimore Class IV?

Many medically relevant groups like picornaviruses (polio, hepatitis A, foot & mouth disease) and astroviruses also possess +ssRNA. Their shared genomic traits lead to rapid emergence and evolution.

How might SARS-CoV-3 be classified if it emerges?

As SARS-CoV-1 & -2 are both group IV coronaviruses, the next related coronavirus would almost certainly remain Baltimore Class IV with a +ssRNA genome. Any deviations would likely represent minor subsystem differences.

Conclusion and Key Takeaways

In summary, key points regarding the Baltimore classification of SARS-CoV-2:

  • Baltimore system categorizes viruses by nucleic acid genome and replication
  • Seven groups designated I-VII established in 1971
  • Remains robust framework for taxonomy five decades later
  • SARS-CoV-2 is a positive-sense ssRNA virus – Baltimore group IV
  • Confers advantage in rapid adaptation and mutation
  • Explains emergence of zoonotic coronaviruses
  • Genomic properties won’t change, but mutations continuously evolve

The enduring legacy of the Baltimore system speaks to the insights it provides on fundamental viral biology. Locating SARS-CoV-2 within this landscape helps guide understanding and ongoing research given its continued global impact.



  1. Culver, James N., and Marty Williams. “The Baltimore Classification System: 50 Years Later—a Tribute to David Baltimore.” Archives of Virology, vol. 166, no. 9, Springer Vienna, Sept. 2021, pp. 2399–414., doi:10.1007/s00705-021-05088-x.
  2. Koonin, Eugene V., et al. “The Baltimore Classification of Viruses: 50 Years Later.” Archives of Virology, vol. 166, no. 4, Springer Vienna, Apr. 2021, pp. 913–42., doi:10.1007/s00705-020-04907-0.
  3. Culver, James, et al. “Virus Taxonomy: The Database, the Class System, and Considerations in Nomenclature.” Phytopathology, vol. 111, no. 11, 2021, pp. 1790–802, doi:10.1094/PHYTO-05-21-0214-IA.
  4. Lauber, Chris, et al. “SARS-CoV-2 Is a Baltimore Class IV Genome Positive-Sense RNA Virus.” Frontiers in Virology, vol. 2, Frontiers Media S.A., 2021, doi:10.3389/fviro.2021.593961.
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