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Question:

A 22-year-old man with fever and joint pain is found to have atypical lymphocytes on his blood smear.  Further evaluation shows that his condition is caused by an enveloped virus containing partially double-stranded circular DNA.  An enzyme packed in its virion has RNA-dependent DNA-polymerase activity.  This patient is most likely infected with which of the following viruses?

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This patient's fever and joint pain are nonspecific symptoms of a viral infection.  Atypical (reactive) lymphocytes are also nonspecific and are seen with many viral infections (although Epstein-Barr virus and cytomegalovirus usually present with the highest counts).

Based on the described viral morphology, this patient is most likely infected with the hepatitis B virus (HBV), a member of the DNA-containing Hepadnaviridae family.  The mature virion (called a Dane particle) consists of a hexagonal protein core (capsid) covered with a lipid bilayer envelope studded with proteins and carbohydrates.  The HBV genome is a partially double-stranded circular DNA molecule housed within the capsid.

After the virion enters the cell, the capsid is released into the cytoplasm and the viral genome is transferred into the nucleus.  The viral DNA is then repaired to form a fully double-stranded circular minichromosome that is capable of being transcribed into viral mRNAs.  Replication of the genome occurs within a newly synthesized capsid containing the full-length viral mRNA transcript.  Reverse transcriptase (which has both RNA- and DNA-dependent DNA-polymerase activity) acts on this RNA template to create a single-stranded DNA intermediate that is then converted back into circular, partially double-stranded DNA.  The mature capsid is then enveloped by a portion of the endoplasmic reticulum containing virally-coded proteins to form the completed virion.

(Choice A)  Coxsackie virus is within the Picornaviridae family and is composed of an icosahedral nucleocapsid and a + single-stranded RNA genome.  The RNA has a protein on the 5' end that acts as a primer for transcription by RNA-dependent RNA polymerase.

(Choices B and C)  Cytomegalovirus and Epstein-Barr virus are members of the Herpesviridae family.  All viruses within this family contain an icosahedral core surrounded by a lipoprotein envelope and have double-stranded, linear DNA.  These are the only viruses to acquire their envelopes by budding from the nuclear membrane.

(Choice E)  Human immunodeficiency virus is within the Lentivirus subgroup of retroviruses.  It contains a bar-shaped protein core surrounded by a glycoprotein envelope that includes the gp120 and gp41 glycoproteins.  The genome is diploid, consisting of 2 + single-stranded RNA molecules that are transcribed into double-stranded DNA by a reverse transcriptase present in the capsid.

(Choice F)  Parvovirus B19 is a small nonenveloped icosahedral virus with a linear, single-stranded DNA genome.  There is no polymerase in the virion.

Educational objective:
Replication of the hepatitis B genome occurs within a newly synthesized capsid through the action of reverse transcriptase on an RNA template.  The mature capsid contains partially double-stranded circular DNA and reverse transcriptase.