A 27-year-old man comes to the emergency department due to 2 weeks of low-grade fever, malaise, and loss of appetite. The patient has no prior medical conditions and takes no medications. He does not smoke cigarettes or drink alcohol but regularly injects illicit drugs. The patient is sexually active and uses condoms inconsistently. Physical examination reveals scleral icterus. A smooth and mildly tender liver edge is palpable 4 cm below the right costal margin. Laboratory results are as follows: Which of the following is an essential step in the replication cycle of the virus infecting this patient?

Question

A 27-year-old man comes to the emergency department due to 2 weeks of low-grade fever, malaise, and loss of appetite.  The patient has no prior medical conditions and takes no medications.  He does not smoke cigarettes or drink alcohol but regularly injects illicit drugs.  The patient is sexually active and uses condoms inconsistently.  Physical examination reveals scleral icterus.  A smooth and mildly tender liver edge is palpable 4 cm below the right costal margin.  Laboratory results are as follows:  Which of the following is an essential step in the replication cycle of the virus infecting this patient?

Quizplus · Accepted Answer

11ec160b_382f_7bd5_9249_1bf59cc94739_MD0001_00 Acute hepatitis B virus (HBV) infection is associated with the shedding of viral antigens (HBsAg, HBeAg) and HBV DNA into the bloodstream and the development of IgM antibodies against HBc. Patients are often asymptomatic, but a minority develops constitutional symptoms (eg, fatigue, loss of appetite), hepatomegaly, icterus, and significant elevations in aminotransferase levels. Transmission in low-prevalence countries (eg, United States) is usually due to injection drug use or unprotected sex. HBV is an encapsulated virus with a partially double-stranded DNA genome. It binds to and enters hepatocytes using a host cell bile salt transporter and then sheds its coat in the host cytoplasm. The partially double-stranded genome is "repaired" and transcribed by host cell machinery, yielding a + sense single-stranded mRNA template. This serves as a pre-genome for future progeny; it is converted by viral reverse transcriptase into the partially double-stranded DNA genome of budding viral particles (which are subsequently released from the cell). The mRNA template is also translated by host ribosomes into the proteins that compose the virus. (Choice A) Both hepatitis C virus and HIV encode for a viral protease that cleaves viral polyprotein into individual proteins. Protease inhibitors target this step in viral replication and are used for treatment. HBV does not generate a polyprotein; therefore, it does not encode for a viral protease. (Choice B) Herpes simplex virus type 1 establishes a life-long latent infection within sensory neurons where it expresses latency-associated transcript, a non-protein coding RNA molecule that suppresses viral lytic genes and inhibits host cell apoptosis. (Choice C) Although HBV can insert its genome into host chromosomes (which contributes to hepatocarcinogenesis), this step is not required for viral replication. In contrast, HIV must integrate into the host genome in order to replicate. Integrase inhibitors (eg, dolutegravir) target this step in HIV replication. (Choice D) HBV is released via exocytosis from host cells and is not considered a lytic virus. Hepatocyte damage occurs primarily when cytotoxic T cells recognize HBV antigens on infected cells. Patients who clear the virus have a robust, polyclonal, cytotoxic T-cell response. Those that develop latent infection often have a much weaker and narrower cytotoxic T-cell response. Educational objective: Hepatitis B virus has a partially double-stranded DNA genome and contains a viral DNA polymerase with reverse transcriptase activity. Reverse transcriptase serves a crucial step in viral replication; it converts transcribed positive sense single-stranded RNA into the partially double-stranded DNA genome of viral progeny. __________ References: Medical virology of hepatitis B: how it began and where we are now. (http://www.ncbi.nlm.nih.gov/pubmed/23870415)

A 27-Year-Old Man Comes to the Emergency Department Due to 2