A 33-year-old male with AIDS and a history of shingles develops a severe, multifocal encephalitis. Therapy is instituted with acyclovir, but the man dies on the fouh day of his hospital admission. Which of the following viruses is the most likely cause of his encephalitis?

**Core Concept**
The question tests the student's knowledge of viral encephalitis, specifically in a patient with a compromised immune system due to AIDS. **Varicella-zoster virus (VZV)** reactivation is a common cause of encephalitis in immunocompromised patients, especially those with a history of shingles.

**Why the Correct Answer is Right**
In this scenario, the patient's history of shingles and AIDS increases his susceptibility to VZV reactivation. VZV causes encephalitis by infecting neurons and glial cells in the brain, leading to inflammation and tissue damage. The virus targets the temporal lobes and other areas of the brain, resulting in severe neurological symptoms. Acyclovir is an antiviral medication that can be effective against VZV, but it is often administered in high doses and for a prolonged period to be effective.

**Why Each Wrong Option is Incorrect**
**Option A:** Herpes simplex virus (HSV) is another common cause of encephalitis, but it is more commonly seen in immunocompetent patients. HSV encephalitis typically affects the temporal lobes and is often associated with seizures and focal neurological deficits.

**Option B:** Cytomegalovirus (CMV) is a common cause of encephalitis in immunocompromised patients, but it is more often seen in patients with HIV/AIDS who have a CD4 count below 100 cells/μL.

**Option C:** Epstein-Barr virus (EBV) is a common cause of infectious mononucleosis, but it is not typically associated with encephalitis.

**Clinical Pearl / High-Yield Fact**
The patient's history of shingles and AIDS increases his susceptibility to VZV reactivation, making VZV encephalitis a medical emergency that requires prompt antiviral therapy.

**Correct Answer:** C. Cytomegalovirus

✓ Correct Answer: D. Herpes zoster-varicella