A diverse virome in kidney transplant patients contains multiple viral subtypes with distinct polymorphisms

Abstract

Recent studies have established that the human urine contains a complex microbiome, including a virome about which little is known. Following immunosuppression in kidney transplant patients, BK polyomavirus (BKV) has been shown to induce nephropathy (BKVN), decreasing graft survival. In this study we investigated the urine virome profile of BKV+ and BKV− kidney transplant recipients. Virus-like particles were stained to confirm the presence of VLP in the urine samples. Metagenomic DNA was purified, and the virome profile was analyzed using metagenomic shotgun sequencing. While the BK virus was predominant in the BKV+ group, it was also found in the BKV− group patients. Additional viruses were also detected in all patients, notably including JC virus (JCV) and Torque teno virus (TTV) and interestingly, we detected multiple subtypes of the BKV, JCV and TTV. Analysis of the BKV subtypes showed that nucleotide polymorphisms were detected in the VP1, VP2 and Large T Antigen proteins, suggesting potential functional effects for enhanced pathogenicity. Our results demonstrate a complex urinary virome in kidney transplant patients with multiple viruses with several distinct subtypes warranting further analysis of virus subtypes in immunosuppressed hosts.

Prevalence of antibodies against BKPyV subtype I and IV in kidney transplant recipients and in the general Czech population

“…The reactivity of antibodies from some samples with both BKPyV‐I and BKPyV‐IV antigens might also result from coinfection with both BKPyV‐subtypes. A recent survey of the virome in a KTx patient revealed that multiple different BKPyV subtypes can coexist at relatively high abundance in a single patient . In agreement with Pastrana et al, the increased seroprevalence of BKPyV‐IV infection was observed in KTx recipients compared to the general population (20% vs 9%, P = 0.051), but the groups were not matched by age.…”

MKPV (aka MuCPV) and related chapparvoviruses are nephro-tropic and encode novel accessory proteins p15 and NS2

“…However, we found none within the datasets. Indeed, we found no parvoviral sequences of any sort within the datasets, as originally reported (34). This limited sample suggests that human kidney chapparvoviral infection is not widespread -at least not in the USA, but it will nonetheless be worthwhile to determine if antibodies against chapparvoviral VP1 antigens are present in human populations.…”

Evaluating bacterial and functional diversity of human gut microbiota by complementary metagenomics and metatranscriptomics

“…The purpose of the study was 5 twofold, first to evaluate the bacterial diversity and differential gene expression of gut microbiota using 6 complementary shotgun metagenomics (MG) and metatranscriptomics (MT) from same fecal sample. 7 Second, to compare sequence data using different Illumina platforms and with different sequencing 8 parameters as new sequencers are introduced and determine if the data are comparable on different 9 platforms. In this study, we perform ultra-deep metatranscriptomic shotgun sequencing for a sample that 10 we previously analyzed with metagenomics shotgun sequencing.…”

“…9B). In other words, more than 50% of the variation 6 in the microbial community MT can be explained by MG composition at species level, or conversely, 7 approximately 50% of transcriptional activity is regulated and presumably dependent on host or 8 environmental factors. .…”

“…microbiome has been associated with multiple disease states including obesity,12 inflammatory bowel disease, asthma, urinary tract infection, cardiovascular disease and cancer (Pflughoeft Versalovic 2012, Rani et al 2016a,Rani et al 2016b). However, the biological mechanisms that link the 14 complex community of a microbiota with the pathogenesis of most diseases remains elusive.…”