Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies.
BACKGROUND
Xenotropic Murine Leukemia Virus-related Virus (XMRV) is a human gammaretrovirus recently identified in prostate cancer tissue and in lymphocytes of patients with chronic fatigue syndrome. To establish the etiologic role of XMRV infection in human disease requires large scale epidemiologic studies. Development of assays to detect XMRV-specific antibodies would greatly facilitate such studies. However, the nature and kinetics of the antibody response to XMRV infection have yet to be determined.


RESULTS
Three rhesus macaques were infected with XMRV to determine the dynamics of the antibody responses elicited by infection with XMRV. All macaques developed antibodies to XMRV during the second week of infection, and the predominant responses were to the envelope protein gp70, transmembrane protein p15E, and capsid protein p30. In general, antibody responses to gp70 and p15E appeared early with higher titers than to p30, especially in the early period of seroconversion. Antibodies to gp70, p15E and p30 persisted to 158 days and were substantially boosted by re-infection, thus, were identified as useful serologic markers. Three high-throughput prototype assays were developed using recombinant proteins to detect antibodies to these viral proteins. Both gp70 and p15E prototype assays demonstrated 100% sensitivity by detecting all Western blot (WB) positive serial bleeds from the XMRV-infected macaques and good specificity (99.5-99.9%) with blood donors. Seroconversion sensitivity and specificity of the p30 prototype assay were 92% and 99.4% respectively.


CONCLUSIONS
This study provides the first demonstration of seroconversion patterns elicited by XMRV infection. The nature and kinetics of antibody responses to XMRV in primates were fully characterized. Moreover, key serologic markers useful for detection of XMRV infection were identified. Three prototype immunoassays were developed to detect XMRV-specific antibodies. These assays demonstrated good sensitivity and specificity; thus, they will facilitate large scale epidemiologic studies of XMRV infection in humans.
Qiu
Xiaoxing
X
Infectious Diseases R&D, Abbott Diagnostics, 100 Abbott Park Rd, Abbott Park, IL 60064, USA. xiaoxing.qiu@abbott.com
Swanson
Priscilla
P
Luk
Ka-Cheung
KC
Tu
Bailin
B
Villinger
Francois
F
Das Gupta
Jaydip
J
Silverman
Robert H
RH
Klein
Eric A
EA
Devare
Sushil
S
Schochetman
Gerald
G
Hackett
John
J
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D004195:Disease Models, Animal; D016021:Epidemiologic Studies; D005260:Female; D017988:Gammaretrovirus / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008253:Macaca mulatta; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology; D012192:Retroviridae Infections / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D012680:Sensitivity and Specificity; D015678:Viral Structural Proteins / Q000276:immunology; D014773:Virology / Q000379:methods*
D000914:Antibodies, Viral; D011994:Recombinant Proteins; D015678:Viral Structural Proteins