Reversal of human immunodeficiency virus type 1 IIIB to a neutralization-resistant phenotype in an accidentally infected laboratory worker with a progressive clinical course.
The role of humoral immunity in controlling human immunodeficiency virus type 1 (HIV-1) is still controversial. The resistance of primary HIV-1 variants to neutralization by antibodies, sera from HIV-1-infected patients, and soluble CD4 protein has been suggested to be a prerequisite for the virus to establish persistence in vivo. To further test this hypothesis, we studied the neutralization sensitivity of two IIIB/LAV variants that were isolated from a laboratory worker who accidentally was infected with the T-cell-line-adapted neutralization-sensitive IIIB isolate. Compared to the original virus in the inoculum, the reisolated viruses showed an increased resistance to neutralization over time. The ratio of nonsynonymous to synonymous nucleotide substitutions in the envelope gene pointed to strong positive selection. The emergence of neutralization-resistant HIV preceded disease development in this laboratory worker. Our results imply that the neutralization resistance of primary HIV may indeed be considered an escape mechanism from humoral immune control.
Beaumont
T
T
Department of Clinical Viro-Immunology, CLB Sanquin, and Laboratory for Experimental and Clinical Immunology, Amsterdam, The Netherlands.
van Nuenen
A
A
Broersen
S
S
Blattner
W A
WA
Lukashov
V V
VV
Schuitemaker
H
H
D000595:Amino Acid Sequence; D002460:Cell Line; D018450:Disease Progression; D015686:Gene Products, env / Q000737:chemistry; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008264:Macrophages / Q000821:virology; D017056:Medical Laboratory Personnel; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016273:Occupational Exposure; D010641:Phenotype; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D017422:Sequence Analysis, DNA
D015686:Gene Products, env; D015483:HIV Antibodies; D019713:Receptors, CCR5; D019718:Receptors, CXCR4