Human pegivirus-1 in the CSF of patients with HIV-associated neurocognitive disorder (HAND) may be derived from blood in highly viraemic patients

Abstract

BackgroundHuman pegivirus-1 (HPgV-1) infection in the brain has not been extensively examined and its association with disease remains unconfirmed. In a high throughput sequencing study to look for infectious agents that could play a role in HIV-associated neurocognitive disorder (HAND), this virus was detected in 3 of 8 CSF samples. ObjectivesTo determine the significance of this finding, additional patients were screened and the viral load and viral diversity in blood and CSF were examined. Study designNested PCR of the viral 5′NCR region was performed on blood and CSF pairs from 16 HAND patients. PCR products were cloned, sequenced and analysed to determine viral diversity in blood and CSF. HPgV-1 viral loads were determined in paired blood and CSF of 2 patients by digital droplet PCR. Nested PCR was also performed on CSF samples from patients with other brain disorders. ResultsVirus was detected in both blood and CSF in 3 of 16 HAND patients. Viral loads were very high in blood (8.81 and 10.56 log copies/ml) and 4–5 logs lower in CSF (4.68 and 5.84 log copies/ml). Sequence analysis of 5′NCR clones in blood and CSF showed limited variation. The dominant viral variant (based on clonal sequence identity) in blood and CSF was usually identical. HPgV-1 was detected in CSF from patients with other brain disorders at a similar frequency (15% versus 18.75% in HAND patients). ConclusionWhile several studies have reported HPgV-1 detection in CSF of patients with brain disease, this is the only study that has examined both blood and CSF compartments simultaneously. Our findings show that virus in CSF always coincided with viraemia and levels were 4–5 logs higher in blood. While a rare, but specific brain tropism cannot be excluded, blood is the more probable source of virus in HAND patients.