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1
Question:

A 36-year-old man comes to the office due to 2 months of fatigue, intermittent arthralgias, and poor appetite.  The patient has no prior medical conditions and takes no medications.  He does not use tobacco or illicit drugs, and he drinks alcohol occasionally.  The patient has had multiple sexual partners and uses condoms inconsistently.  Physical examination shows no abnormalities.  Liver aminotransferases are elevated.  Hepatitis serology shows the following:

Hepatitis A virus antibody, totalnegative
Hepatitis B surface antibody (HBsAb)negative
Hepatitis B core antibody (HBcAb), totalpositive
Hepatitis B surface antigen (HBsAg)positive
Hepatitis B E antigen (HBeAg)positive
Hepatitis C virus antibodynegative

Which of the following genome replicative processes is most likely used by the virus infecting this patient?

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Explanation:

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Acute hepatitis B virus (HBV) infection is marked by the presence of HBsAg, HBeAg, and anti-HBc, and a lack of anti-HBs.  Infections are often asymptomatic, but many patients have a few months of jaundice, fatigue, nausea, and right upper–quadrant discomfort.  Perinatal transmission is most common in high-prevalence countries (eg, Sub-Saharan Africa); in low-prevalence regions (eg, United States), most cases occur due to unprotected sex or intravenous drug use.

HBV is a hepadnavirus composed of:

  • an outer lipid envelope that contains viral-encoded proteins (HBsAg) and host lipid components.

  • an icosahedral nucleocapsid core that contains a circular, partially double-stranded DNA genome and a DNA polymerase with reverse transcriptase activity.

HBV binds to a bile salt transporter on the surface of hepatocytes and enters the cell.  After the virus is uncoated in the host cytoplasm, the single-stranded DNA portion of the viral genome is completed (repaired) by cellular DNA polymerases.  This generates double-stranded viral DNA, which is subsequently transcribed by host RNA polymerase into a +single-stranded RNA pregenome.  The +RNA template is then translated into the proteins that compose the virus (eg, envelope, core, polymerase); it is also converted by viral DNA polymerase/reverse transcriptase into the partially double-stranded DNA progeny of developing viral particles.

(Choice A)  This replicative sequence characterizes adenovirus, herpesvirus, and poxvirus.

(Choice C)  This replicative sequence characterizes parvovirus B19.

(Choice D)  This replicative sequence characterizes the retroviruses (eg, HIV).

(Choice E)  This replicative sequence characterizes poliovirus.

(Choice F)  This replicative sequence characterizes influenza virus, measles virus, and rabies virus.

Educational objective:
The hepatitis B virus (HBV) replicates via the following sequence: double-stranded DNA → +RNA template → partially double-stranded DNA progeny.  Although it is a DNA virus, HBV uses reverse transcription to generate new viral DNA from a positive-sense RNA template.