Baltimore Classification of Viruses Amended

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Are you aware that the Baltimore Classification of Viruses has just been modified again? A significant number of viruses have been reclassified under new viral families. If you graduated from med school more than year ago, then you are unlikely to be familiar with these new principles. This is made difficult by the fact that textbooks only get updated every 3-4 years and are unlikely to reflect the changes that just occurred.

If you need help navigating your way through these critically essential and challenging principles on the USMLE, visit and sign up for the USMLE Insider online course. Our experts got all the concepts and answers.

Check out one of our USMLE questions on these concepts. This is one of the questions our students receive following our Microbiology lectures. Test yourself with this and let us see how you do. We will discuss the answer and offer explanations later.

1. A 55-year-old previously healthy Utah farmer presents to the hospital in the summer complaining of a four-day history of fever, chills, severe muscle aches, and persistent non-productive cough. Upon examination, his breathing is found to be labored. He denies any history of smoking. He mentions that he tore down an old barn on his property 2 weeks ago because of its colonization by mice. Investigation shows bilateral pleural effusion and pulmonary edema in a patient with pronounced clinical lung manifestations. Laboratory studies show elevated serum lactate dehydrogenase and aspartate transaminase, decreased platelet count, and increased hematocrit. A member of which of the following viral families is the most likely causative agent for this patient's disease?

A. Arenaviridae
B. Coronaviridae
C. Hantaviridae
D. Phenuiviridae
E. Peribunyaviridae
F. Picornaviridae
G. Reoviridae


The answer is C. This is a classic case of Hantavirus cardiopulmonary syndrome (HCPS). Early symptoms that are universal include fatigue, fever and myalgias. There may also be headaches, dizziness, chills, and gastrointestinal distress, such as nausea, vomiting, diarrhea, and abdominal pain.

About half of all HPS patients experience these symptoms. Four to 10 days after the initial phase of illness, the late symptoms of HPS appear. These include coughing and shortness of breath, with the sensation of chest tightness. The respiratory failure may be unresponsive to 100% oxygen therapy.

Radiography classically shows bilateral pleural effusion that is characteristic of the mid-stage of this syndrome. The radiological evolution of HPS begins with minimal changes of interstitial pulmonary edema, progressing to alveolar edema with severe bilateral involvement. Pleural effusions are common and are often large enough to be evident radiographically.

Hantavirus, which was previously classified under the Bunyaviridae family of viruses, was first isolated from deer mice in the Four Corners region, which encompasses parts of Arizona, Colorado, New Mexico and Utah, following an outbreak of the disease in that area in 1993.

Sin Nombre virus (Spanish for 'the virus with no name') is the prototypical New World Hantavirus and is the cause of the vast majority of cases of HCPS in the United States. Other hantaviruses (such as the Seoul, Puumala, and Dobrava hantaviruses) are responsible for causing HCPS in other parts of the world.

Rodents are the natural hosts and infected rodents shed the virus in their saliva, urine, and feces for several weeks. Humans can contract the disease when they breathe in aerosolized virus.

Bunyavirales is an order of negative-sense single-stranded RNA viruses. It was formerly known as Bunyaviridae family of viruses. All five genera formerly in the family Bunyaviridae (Hantavirus, Nairovirus, Orthobunyavirus, Phlebovirus, Tospovirus) are now novel viral families, some of which have been combined. These new families include: Hantaviridae, Feraviridae, Fimoviridae, Jonviridae, Nairoviridae, Peribunyaviridae, Phasmaviridae, Phenuiviridae, and Tospoviridae. The ones causing disease in humans are highlighted in bold.

The Table below summarizes the former Bunyaviridae virus families of clinical significance. The new family names are shown. The most important ones for the USMLE are highlighted in bold.

Bunyavirales Agents That Cause Disease in Humans
Virus Family Reservoir Vector Amplifying Hosts

California encephalitis virus 

La Crosse encephalitis virus 

Jamestown Canyon virus

Snowshoe hare virus 




Bwamba Fever Peribunyaviridae Monkeys Mosquitoes  Donkeys
Hantavirus Hantaviridae Small mammals or rodents  Aerosolized excreta from these mammals   
Crimean-Congo hemorrhagic fever Nairoviridae Ticks Ticks, small mammals, domestic mammals Small mammals, domestic mammals
Rift Valley fever  Phenuiviridae Bats Mosquitoes Small mammals, domestic mammals

Lassa fever virus

Argentine hemorrhagic fever 

Arenaviridae Rodents Aerosolized excreta from these mammals  
Huaiyangshan banyangvirus (formerly SFTS* virus)   Phenuiviridae    Ticks  
 *SFTS, severe fever with thrombocytopenia syndrome

(Choice A) Arenaviridae members include Lassa fever virus (which causes hemorrhagic fever in West Africa) and lymphocytic choriomeningitis virus (which is imported from South America and causes influenza-like disease with meningeal signs).

(Choice B) Coronaviridae members include the coronaviruses that cause the common cold, such as Human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 (both members of the Betacoronavirus genus), and Human coronavirus 229E and HCoV-NL63 (members of the Alphacoronavirus genus). Other members include Middle East respiratory syndrome-related coronavirus (MERS-CoV), which causes MERS; Severe acute respiratory syndrome coronavirus (SARS-CoV), which caused SARS pandemic of 2002-2004; and SARS-CoV-2, which causes COVID-19.

(Choice D) Rift Valley fever virus (RVFV) and Huaiyangshan banyangvirus (formerly severe fever with thrombocytopenia syndrome [SFTS] virus) are the species of the Phlebovirus genus of the Phenuiviridae family in the order Bunyavirales. RVFV is the virus that causes rift valley fever (RVF), a disease that occurs across sub-Saharan Africa. The Huaiyangshan banyangvirus causes the clinical condition known as severe fever with thrombocytopenia syndrome (SFTS), which is an emerging disease in Asia. 

(Choice E) Peribunyaviridae members include the California encephalitis virus and the La Crosse encephalitis virus, which cause encephalitis.

(Choice F) Picornaviridae include poliovirus, echovirus, rhinovirus, coxsackie viruses, and hepatitis A.

(Choice G) Reoviridae family includes Colorado tick fever virus, reovirus, and rotavirus.


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