A single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with the ability to cause growth hormone deficiency syndrome

Persistent infection of C3H/St mice with certain strains of lymphocytic choriomeningitis virus (LCMV) causes a growth hormone (GH) deficiency syndrome (GHDS) manifested as growth retardation and hypoglycemia, Infected mice show high levels of viral replication in the GH-producing cells in the anterior pituitary leading to dea eased synthesis of GH mRNA and protein despite the absence of detectable virus-induced cell structural damage, Virus clones isolated from the GHDS-negative LCMV WE strain can cause the disease, while others cannot, The genetic basis of this phenotypic difference is a nucleotide substitution resulting in a single amino acid difference in the vital glycoprotein. Reassortant studies indicate that the single amino acid substitution (Ser-153 to Phe) is sufficient to allow infection of the GH-producing cells and cause GHDS. These results show that a single change in the genome can affect viral pathogenicity by altering the tropism of the virus.