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 decreased 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 viral 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.
Teng
M N
MN
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Borrow
P
P
Oldstone
M B
MB
de la Torre
J C
JC
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics*; D006130:Growth Disorders / Q000821:virology*; D007003:Hypoglycemia / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D008809:Mice, Inbred C3H; D010649:Phenylalanine; D016865:Reassortant Viruses; D012694:Serine; D013577:Syndrome; D014764:Viral Proteins / Q000235:genetics*
D006023:Glycoproteins; D014764:Viral Proteins; D012694:Serine; D010649:Phenylalanine