Viruses

Viruses US Medical PG Question 1: An HIV-positive 48-year-old man comes to the emergency department because of a 3-month history of recurrent, painful mouth ulcers. This time, the pain is so severe that the patient cannot eat. He has a history of a seizure disorder but currently does not take any medications. He appears very ill. His temperature is 39.0°C (102.2°F). Physical examination shows numerous vesicular ulcerations on the lips and sloughing of the gums, buccal mucosa, and hard palate. Genetic analysis of the pathogen isolated from the lesions shows a mutation in a gene encoding viral phosphotransferases. Which of the following drugs is the most appropriate treatment?

• A. Acyclovir
• B. Famciclovir
• C. Cidofovir
• D. Ganciclovir
• E. Foscarnet (Correct Answer)

Viruses Explanation: ***Foscarnet*** - The presence of **recurrent, painful vesicular ulcerations** in an HIV-positive patient, especially with **gingivostomatitis-like symptoms** (sloughing gums, buccal mucosa), points to a severe **herpes simplex virus (HSV) infection**, likely resistant to nucleoside analogues given the **phosphotransferase mutation**. - **Foscarnet** is a pyrophosphate analog that directly inhibits viral DNA polymerase without requiring phosphorylation by viral thymidine kinase, making it effective against **acyclovir-resistant HSV** strains, which often develop resistance via mutations in viral phosphotransferases or thymidine kinase. *Acyclovir* - **Acyclovir** is a nucleoside analog that requires phosphorylation by viral thymidine kinase (a phosphotransferase) to become active. - A **mutation in viral phosphotransferases** would render the virus resistant to acyclovir, making it an ineffective treatment. *Famciclovir* - **Famciclovir** is a prodrug of penciclovir, which is also a nucleoside analog that requires phosphorylation by viral thymidine kinase for activation. - Similar to acyclovir, a **mutation in viral phosphotransferases** would lead to resistance and make famciclovir ineffective. *Cidofovir* - **Cidofovir** is a nucleotide analog that does not require phosphorylation by viral enzymes for its initial activation. - While it can be effective against some resistant strains, **foscarnet is generally preferred** for severe, resistant HSV infections as cidofovir is primarily used for **CMV retinitis** and is associated with significant nephrotoxicity. *Ganciclovir* - **Ganciclovir** is a nucleoside analog primarily used for **CMV infections**, and it also requires phosphorylation by viral kinases for activation. - It is not the first-line treatment for HSV, and the **phosphotransferase mutation** would likely confer resistance to ganciclovir as well.

Viruses US Medical PG Question 2: A scientist in Boston is studying a new blood test to detect Ab to the parainfluenza virus with increased sensitivity and specificity. So far, her best attempt at creating such an exam reached 82% sensitivity and 88% specificity. She is hoping to increase these numbers by at least 2 percent for each value. After several years of work, she believes that she has actually managed to reach a sensitivity and specificity even greater than what she had originally hoped for. She travels to South America to begin testing her newest blood test. She finds 2,000 patients who are willing to participate in her study. Of the 2,000 patients, 1,200 of them are known to be infected with the parainfluenza virus. The scientist tests these 1,200 patients’ blood and finds that only 120 of them tested negative with her new test. Of the following options, which describes the sensitivity of the test?

• A. 82%
• B. 86%
• C. 98%
• D. 90% (Correct Answer)
• E. 84%

Viruses Explanation: ***90%*** - **Sensitivity** is calculated as the number of **true positives** divided by the total number of individuals with the disease (true positives + false negatives). - In this scenario, there were 1200 infected patients (total diseased), and 120 of them tested negative (false negatives). Therefore, 1200 - 120 = 1080 patients tested positive (true positives). The sensitivity is 1080 / 1200 = 0.90, or **90%**. *82%* - This value was the **original sensitivity** of the test before the scientist improved it. - The question states that the scientist believes she has achieved a sensitivity "even greater than what she had originally hoped for." *86%* - This value is not directly derivable from the given data for the new test's sensitivity. - It might represent an intermediate calculation or an incorrect interpretation of the provided numbers. *98%* - This would imply only 24 false negatives out of 1200 true disease cases, which is not the case (120 false negatives). - A sensitivity of 98% would be significantly higher than the calculated 90% and the initial stated values. *84%* - This value is not derived from the presented data regarding the new test's performance. - It could be mistaken for an attempt to add 2% to the original 82% sensitivity, but the actual data from the new test should be used.

Viruses US Medical PG Question 3: A 27-year-old woman who recently emigrated from Brazil comes to the physician because of fever, fatigue, decreased appetite, and mild abdominal discomfort. She has not seen a physician in several years and her immunization status is unknown. She drinks 2 alcoholic beverages on the weekends and does not use illicit drugs. She is sexually active with several male partners and uses condoms inconsistently. Her temperature is 38°C (99.8°F). Physical examination shows right upper quadrant tenderness and scleral icterus. Serology confirms acute infection with a virus that has partially double-stranded, circular DNA. Which of the following is most likely involved in the replication cycle of this virus?

• A. Adhesion of virus to host ICAM-1 receptor
• B. Cleavage of gp160 to form envelope glycoprotein
• C. Bacterial translation of viral DNA
• D. Transcription of viral DNA to RNA in the cytoplasm
• E. Reverse transcription of viral RNA to DNA (Correct Answer)

Viruses Explanation: ***Reverse transcription of viral RNA to DNA*** - The description of a virus with **partially double-stranded, circular DNA** that causes acute infection with fever, fatigue, and **scleral icterus** points to **Hepatitis B virus (HBV)**. - HBV is a **hepadnavirus** with a unique replication strategy: despite being a DNA virus, it replicates through an **RNA intermediate** (pregenomic RNA). - The virus uses **reverse transcriptase** to synthesize DNA from this RNA template within the nucleocapsid—making it the only DNA virus that uses reverse transcription in its replication cycle. *Adhesion of virus to host ICAM-1 receptor* - The **intercellular adhesion molecule 1 (ICAM-1) receptor** is primarily used by viruses like **rhinovirus** for entry into host cells, which is not characteristic of HBV. - HBV primarily uses the **sodium taurocholate co-transporting polypeptide (NTCP)** as its entry receptor on hepatocytes. *Cleavage of gp160 to form envelope glycoprotein* - **gp160** is a precursor protein of the **HIV envelope glycoprotein**, which is cleaved into gp120 and gp41, essential for HIV entry. - This process is specific to **retroviruses** like HIV and is not involved in HBV replication. *Bacterial translation of viral DNA* - Viruses, including HBV, replicate within **eukaryotic host cells** and utilize the host cell's machinery for replication, transcription, and translation. - **Bacterial translation** is irrelevant to viral replication in human hosts. *Transcription of viral DNA to RNA in the cytoplasm* - While transcription of viral DNA to RNA does occur in HBV, it primarily takes place in the **nucleus** of the host hepatocyte, not the cytoplasm. - The resulting pregenomic RNA is then exported to the cytoplasm for **reverse transcription** within newly assembled nucleocapsids.

Viruses US Medical PG Question 4: A 40-year-old man presents with problems with his vision. He says he has been experiencing blurred vision and floaters in his left eye for the past few days. He denies any ocular pain, fever, or headaches. Past medical history is significant for HIV infection a few years ago, for which he is noncompliant with his antiretroviral medications and his most recent CD4 count was 100 cells/mm3. His temperature is 36.5°C (97.7°F), the blood pressure is 110/89 mm Hg, the pulse rate is 70/min, and the respiratory rate is 14/min. Ocular exam reveals a decreased vision in the left eye, and a funduscopic examination is shown in the image. The patient is admitted and immediately started on intravenous ganciclovir. A few days after admission he is still complaining of blurry vision and floaters, so he is switched to a different medication. Inhibition of which of the following processes best describes the mechanism of action of the newly added medication?

• A. Protein synthesis
• B. Nucleic acid synthesis (Correct Answer)
• C. Progeny virus release
• D. Viral penetration into host cells
• E. Viral uncoating

Viruses Explanation: ***Nucleic acid synthesis*** - This patient likely has **cytomegalovirus (CMV) retinitis**, characterized by **blurred vision**, **floaters**, and **necrotizing retinitis** in an HIV-positive individual with a **low CD4 count (100 cells/mm3)**. - The initial drug, **ganciclovir**, targets nucleic acid synthesis by inhibiting viral DNA polymerase. If ganciclovir fails, a common second-line agent like **foscarnet** or **cidofovir** is used, and both also inhibit viral **nucleic acid (DNA) synthesis** through different mechanisms (foscarnet directly inhibits DNA polymerase, cidofovir is a nucleotide analog). *Protein synthesis* - This mechanism is targeted by certain antibacterial and antifungal drugs, but not typically by antiviral medications used for CMV. - Antiviral drugs generally target specific viral processes, distinct from host protein synthesis, to limit toxicity. *Progeny virus release* - This mechanism is primarily targeted by **neuraminidase inhibitors** (e.g., oseltamivir, zanamivir) used to treat influenza, which prevent the release of new viral particles from infected cells. - It is not a common mechanism for CMV antivirals. *Viral penetration into host cells* - Medications that inhibit viral penetration or entry, such as **fusion inhibitors** (e.g., enfuvirtide for HIV) or **CCR5 antagonists** (e.g., maraviroc for HIV), prevent the virus from entering the host cell. - These mechanisms are not relevant to the treatment of CMV retinitis. *Viral uncoating* - **Amantadine** and **rimantadine** are examples of antiviral drugs that inhibit **viral uncoating** by interfering with the M2 ion channel in influenza A. - This mechanism is specific to influenza viruses and is not involved in the action of CMV antiviral medications.

Viruses US Medical PG Question 5: A 30-year-old forest landscape specialist is brought to the emergency department with hematemesis and confusion. One week ago she was diagnosed with influenza when she had fevers, severe headaches, myalgias, hip and shoulder pain, and a maculopapular rash. After a day of relative remission, she developed abdominal pain, vomiting, and diarrhea. A single episode of hematemesis occurred prior to admission. Two weeks ago she visited rainforests and caves in western Africa where she had direct contact with animals, including apes. She has no history of serious illnesses or use of medications. She is restless. Her temperature is 38.0℃ (100.4℉); the pulse is 95/min, the respiratory rate is 20/min; and supine and upright blood pressure is 130/70 mm Hg and 100/65 mm Hg, respectively. Conjunctival suffusion is noted. Ecchymoses are observed on the lower extremities. She is bleeding from one of her intravenous lines. The peripheral blood smear is negative for organisms. Filovirus genomes were detected during a reverse transcription-polymerase chain reaction. The laboratory studies show the following: Laboratory test Hemoglobin 10 g/dL Leukocyte count 1,000/mm3 Segmented neutrophils 65% Lymphocytes 20% Platelet count 50,000/mm3 Partial thromboplastin time (activated) 60 seconds Prothrombin time 25 seconds Fibrin split products positive Serum Alanine aminotransferase (ALT) 85 U/L Aspartate aminotransferase (AST) 120 U/L γ-Glutamyltransferase (GGT) 83 U/L Creatinine 2 mg/dL Which of the following is the most appropriate immediate step in management?

• A. Esophagogastroduodenoscopy
• B. Postexposure vaccination of close contacts
• C. Parenteral artesunate plus sulfadoxine/pyrimethamine
• D. Use of N95 masks
• E. Intravenous fluids and electrolytes (Correct Answer)

Viruses Explanation: ***Intravenous fluids and electrolytes*** - The patient presents with **orthostatic hypotension**, internal bleeding (hematemesis, ecchymoses), and deranged renal function (elevated creatinine). These indicate significant **fluid loss** and potential **hypovolemic shock**, making immediate fluid resuscitation critical. - **Ebola virus disease** (indicated by the travel history, symptoms, and positive filovirus genomes) often leads to severe dehydration due to fluid loss from vomiting, diarrhea, and internal bleeding, necessitating aggressive fluid and electrolyte replacement as a cornerstone of supportive care. *Esophagogastroduodenoscopy* - While the patient has hematemesis, her overall clinical picture with **severe coagulopathy** (elevated PT/aPTT, low platelets, positive fibrin split products) and **multisystem involvement** suggests a systemic bleeding disorder rather than a focal upper GI bleed that would be the primary target of an EGD. - Performing an invasive procedure like EGD in a patient with severe coagulopathy and a highly contagious disease like Ebola (implied by filovirus detection) carries significant risks and is not the most immediate priority compared to stabilizing vital signs and correcting fluid deficits. *Postexposure vaccination of close contacts* - This is a crucial public health measure for **Ebola virus disease** but is a secondary step in management focused on prevention for others, not the immediate stabilization or treatment of the acutely ill patient. - While important, it does not address the patient's immediate, life-threatening symptoms of hypovolemia, bleeding, and organ dysfunction. *Parenteral artesunate plus sulfadoxine/pyrimethamine* - This regimen is an antimalarial treatment. While the patient traveled to Western Africa, her symptoms and the detection of **filovirus genomes** rule out malaria as the primary diagnosis requiring this specific treatment. - Administering antimalarials would delay appropriate supportive care for Ebola virus disease and is not indicated given the specific viral diagnosis. *Use of N95 masks* - **N95 masks** are important for healthcare worker protection given the patient's symptoms and confirmed filovirus. However, the question asks for the most appropriate *immediate step in management* of the patient's condition. - While infection control is paramount, providing immediate direct patient care like fluid resuscitation takes precedence for the patient's survival over PPE considerations, assuming adequate PPE is already being donned by healthcare providers.

Viruses Flashcard 1 of 5

Question: Which viral virulence factor promotes the release of progeny virions?_____

Answer: Neuraminidase

Viruses Flashcard 2 of 5

Question: What type of viruses are Flaviviruses? (DNA, RNA (sense), etc.)_____

Answer: Positive sense RNA

Viruses Flashcard 3 of 5

Question: RSV contains the virulence factor _____, which allows the production of multinucleated giant cells

Answer: F (fusion) protein

Viruses Flashcard 4 of 5

Question: _____ is a viral envelope protein that allows for mature virion release

Answer: Neuraminidase

Viruses Flashcard 5 of 5

Question: Filoviruses (ebola, marburg) may be transmitted via _____ or bats

Answer: primates (apes)

Extra Information:  Watch Ebolavirus, Marburgvirus (Filoviridae) [https://dashboard.sketchy.com/study/medical/courses/medical-microbiology/units/medical-microbiology-viruses/videos/medical-microbiology-viruses-rna-viruses-negative-sense-ebolavirus-marburgvirus-filoviridae?utm_source=anki&utm_medium=partnership&utm_campaign=february_update&utm_content=medical] https://onlinemeded.org/spa/infectious-disease?ref=anki