Baltimore system of Classifications of Viruses

The Baltimore system of virus classification devised by virologist & Nobel laureate David Baltimore is based on the genomic nature of the viruses. The central theme of the Baltimore system of virus classification is that all viruses must synthesize positive-strand mRNAs from their genomes to produce proteins and replicate themselves. The precise mechanisms whereby this is achieved differ for each virus family.

Central Dogma of Molecular Biology
Central Dogma

Why + mRNA is placed at the center?

Baltimore’s classification system is based on the central role of the translational machinery, places mRNA in the center, and describes the pathways to form mRNA from DNA or RNA genomes. Viruses can replicate DNA and/or RNA, synthesize RNA from DNA, or vice versa, but lack a complete system to make proteins, for which they have to rely on host cell ribosomes. Host cells, on the other hand, can synthesize proteins only from +mRNA strands. Irrespective of the genomic nature of viruses, all viruses must synthesize viral + mRNAs to produce viral proteins”no exception to date.”

How do you designate positive (+) and/or negative (−) strands?

The mRNA, which can serve as the template for protein synthesis, is defined as a positive (+) strand {by convention (nothing to do with charge/electricity)}. A strand of DNA of the equivalent polarity is also called the (+) strand. RNA and DNA strands complementary to the (+) strands are called negative (−) strands.

Viral genomes can be broken down into seven fundamentally different groups, which require different basic strategies for their replication depending on the nature of their genome. When originally conceived, the Baltimore scheme encompassed six classes of the viral genome. Subsequently, the gapped DNA genome of hepadnaviruses (e.g., hepatitis B virus) was discovered and incorporated into a new scheme.

Viruses can be classified into seven (arbitrary) groups:

Baltimore system of classification of viruses

I.    Double-stranded DNA viruses

Some replicate in the nucleus e.g., adenoviruses using cellular proteins. Poxviruses replicate in the cytoplasm and make their own enzymes for nucleic acid replication . e.g., Adenoviruses; Herpesviruses; Poxviruses, etc

II. Single-stranded (+) sense DNA viruses 

Replication occurs in the nucleus, involving the formation of a (-) sense strand, which serves as a template for (+) strand RNA and DNA synthesis. e.g., Parvoviruses

III. Double-stranded RNA viruses

These viruses have segmented genomes. Each genome segment is transcribed separately to produce monocistronic mRNAs. e.g.,  Reoviruses

IV.  Single-stranded (+) sense RNA viruses  (Picornaviruses; Togaviruses, etc)

  • Polycistronic mRNA:  Genome RNA = mRNA. Since the RNA is in the same sense as mRNA, the RNA alone is infectious, with no virion particle associated with polymerase. Translation results in forming a polyprotein product, which is cleaved to form the mature proteins. e.g. Picornaviruses (poliovirus, rhinovirus); Hepatitis A virus
  • Complex Transcription: Two or more rounds of translation are necessary to produce the genomic RNA .  e.g. Picornaviruses; Hepatitis A.

V. Single-stranded (-) sense RNA viruses 

The virion RNA is a negative sense (complementary to mRNA) and must be copied into the complementary plus-sense mRNA to make proteins. This group of viruses must code for RNA-dependent RNA-polymerase and carry it in the virion to make mRNAs upon infecting the cell. e.g. Orthomyxoviruses, Rhabdoviruses, etc

  • Segmented e.g. Orthomyxoviruses. The first step in replication is a transcription of the (-) sense RNA genome by the virion RNA-dependent RNA polymerase to produce monocistronic mRNAs, which also serve as the template for genome replication.
  • Non-segmented e.g. Rhabdoviruses. Replication occurs as above, and monocistronic mRNAs are produced.

VI.  Single-stranded (+) sense RNA viruses with DNA intermediate in life-cycle 

RNA genome is (+) sense but unique among viruses in that it is DIPLOID and does not serve as mRNA but as a template for reverse transcription. e.g., Retroviruses.

Retroviruses, therefore, encode an RNA-dependent DNA polymerase (reverse transcriptase) to make the DNA provirus which then is transcribed to genomic RNA by a host enzyme, RNA polymerase II.

VII.  Double-stranded DNA viruses  with RNA intermediate 

This group of viruses also relies on reverse transcription, but unlike the Retroviruses, this occurs inside the virus particle on maturation. On infection of a new cell, the first event is a repair of the gapped genome, followed by a transcription. e.g., Hepadnaviruses

Watch video explanation of Baltimore scheme by renowned virologist Vincent Racaniello.


  1. The elegance of the Baltimore system is “knowing only the nature of the viral genome, one can deduce the basic steps that must take place to produce mRNA”*.

Further Readings

  1. Expression of animal virus genomes by D. Baltimore
  2. * Simplifying virus classification: The Baltimore system by Vincent Racaniello

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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