A 35-year-old man is found to have elevated alanine aminotransferase and aspartate aminotransferase levels. He has no abdominal pain, nausea, or vomiting. The patient has used intravenous drugs in the past but denies significant alcohol use. His past medical history is negative for blood transfusions or excessive acetaminophen use. Physical examination findings are normal. Laboratory studies show high titers of IgG directed against the hepatitis C envelope protein. Which of the following is the most likely reason that these antibodies do not confer effective immunity against the infection?

Question

A 35-year-old man is found to have elevated alanine aminotransferase and aspartate aminotransferase levels.  He has no abdominal pain, nausea, or vomiting.  The patient has used intravenous drugs in the past but denies significant alcohol use.  His past medical history is negative for blood transfusions or excessive acetaminophen use.  Physical examination findings are normal.  Laboratory studies show high titers of IgG directed against the hepatitis C envelope protein.  Which of the following is the most likely reason that these antibodies do not confer effective immunity against the infection?

Quizplus · Accepted Answer

11ec160b_3870_7cc8_9249_ed2313d7ac9d_MD0001_00 Hepatitis C virus (HCV) has 6 or more genotypes and multiple subtypes that differ in genomic composition by as much as 30%-35%. This is largely due to the fact that the virion-encoded RNA-dependent RNA polymerase has no proofreading 3' → 5' exonuclease activity, which results in many errors during replication. Although most patients are infected with a single genotype, the high mutation rate leads to the development of distinct quasispecies within infected individuals over time. These variant strains differ primarily at hypervariable genomic regions, such as those found in the sequences coding for its envelope glycoproteins. The continuous generation of novel envelope glycoproteins prevents infected individuals from mounting an effective immune response. As production of host antibodies against a quasispecies commences, that strain dies off and new ones take its place. The tremendous antigenic variety of HCV has significantly slowed efforts to develop an effective vaccine. (Choices A and B) The envelope proteins of HCV are not lost after recurrent viral replication nor are they sequestered within hepatocytes. These proteins are necessary for viral infectivity as they mediate membrane adhesion and fusion with host hepatocytes. (Choice C) Like most foreign (nonself) proteins, the envelope proteins of HCV are highly immunogenic. (Choice E) Host antibodies against HCV have neutralizing properties and are effective in eliminating more established hepatitis C quasispecies. It is the constantly emerging mutant strains that pose the greatest challenge to the host immune system. Educational objective: Genetic variations created during hepatitis C virus (HCV) replication result in marked variety in the antigenic structure of HCV envelope proteins. The production of host antibodies lags behind that of new mutant HCV strains, preventing infected individuals from mounting an effective immune response. __________ References: Virus-neutralizing antibodies to hepatitis C virus. (http://www.ncbi.nlm.nih.gov/pubmed/23647953) Hepatitis C virus hypervariable region 1 modulates receptor interactions, conceals the CD81 binding site, and protects conserved neutralizing epitopes. (http://www.ncbi.nlm.nih.gov/pubmed/20357091)

A 35-Year-Old Man Is Found to Have Elevated Alanine Aminotransferase