TT virus (TTV) loads associated with different peripheral blood cell types and evidence for TTV replication in activated mononuclear cells

Maggi, Fabrizio; Fornai, Claudia; Zaccaro, Lucia; Morrica, Antonietta; Vatteroni, Maria Linda; Isola, Patrizia; Marchi, Santino; Ricchiuti, Angelo; Pistello, Mauro; Bendinelli, Mauro

doi:10.1002/jmv.1035

Cited by 103 publications

(91 citation statements)

References 27 publications

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“…NK-cells are permissive for vaccinia infection in vitro (Kirwan et al, 2006;Rajagopalan & Long, 2000; Sánchez-Puig et al, 2004) and TTV genomes are present in NK-cells ex vivo (Maggi et al, 2001;Okamoto, 2009; Takahashi et al, 2002;Zhong et al, 2002). We found HPgV RNA in highly purified NKcells obtained from four of five subjects (mean 42 genome equivalents per 10 4 cells) (Chivero et al, 2014).…”

Section: Hpgv and Nk-cellsmentioning

confidence: 73%

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Chivero

Stapleton

2015

Journal of General Virology

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Human pegivirus (HPgV; originally called GB virus C/hepatitis G virus) is an RNA virus within the genus Pegivirus of the family Flaviviridae that commonly causes persistent infection. Worldwide, 750 million people are actively infected (viraemic) and an estimated 0.75-1.5 billion people have evidence of prior HPgV infection. No causal association between HPgV and disease has been identified; however, several studies described a beneficial relationship between persistent HPgV infection and survival in individuals infected with human immunodeficiency virus. The beneficial effect appeared to be related to a reduction in host immune activation. HPgV replicates well in vivo (mean plasma viral loads typically .1¾10 7 genome copies ml -1 ); however, the virus grows poorly in vitro and systems to study this virus are limited. Consequently, mechanisms of viral persistence and host immune modulation remain poorly characterized, and the primary permissive cell type (s) has not yet been identified. HPgV RNA is found in liver, spleen, bone marrow and PBMCs, including Tand B-lymphocytes, NK-cells, and monocytes, although the mechanism of cell-to-cell transmission is unclear. HPgV RNA is also present in serum microvesicles with properties of exosomes. These microvesicles are able to transmit viral RNA to PBMCs in vitro, resulting in productive infection. This review summarizes existing data on HPgV cellular tropism and the effect of HPgV on immune activation in various PBMCs, and discusses how this may influence viral persistence. We conclude that an increased understanding of HPgV replication and immune modulation may provide insights into persistent RNA viral infection of humans. IntroductionHuman pegivirus (HPgV) is an RNA virus within the Pegivirus A species and family Flaviviridae (Adams et al., 2013;Stapleton et al., 2012a). The virus was originally called hepatitis G virus (HGV)/GB virus type C (GBV-C). The letters 'GB' represented the initials of a surgeon with acute hepatitis whose sera caused hepatitis in marmosets (Deinhardt et al., 1967). Subsequent studies found that this virus did not cause hepatitis and there was no direct evidence that the surgeon ('G. B.') was infected with HPgV. Thus, the virus (HGV/GBV-C), along with several related primate and bat viruses (GBV-A, GBV-C czp , GBV-D), was assigned to a new genus (Pegivirus) and renamed as HPgV (Adams et al., 2013;Stapleton et al., 2012a). HPgV has a 9.4 kb positive-sense ssRNA genome that is organized similarly to hepatitis C virus (HCV) (Fig. 1). HPgV and HCV are unusual amongst RNA viruses in that they commonly cause persistent infection in immune-competent humans.Although HPgV is not as efficient at establishing persistent infection as HCV, an estimated 25 % of infections persist and the other 75 % clear viraemia within 2 years of infection (Gutierrez et al., 1997;Tanaka et al., 1998a). The prevalence of HPgV viraemia in cross-sectional serum surveys of healthy blood donors in developed countries is between 1 and 5 %, whilst up to 20 % of blood donors in ...

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Section: Hpgv and Nk-cellsmentioning

confidence: 73%

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Chivero

Stapleton

2015

Journal of General Virology

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“…Prevalence in the plasma is almost universal as primary infection is acquired early in childhood through the respiratory route and is followed by chronic infection leading to stable viraemia. Activated peripheral blood mononuclear cells were soon identified as the main replication-competent cells (Maggi et al, 2001;Mariscal et al, 2002;Okamura et al, 1999). Unfortunately, TTV cannot be cultured yet, although recently the related TTMV has been cultured on respiratory epithelium A549 cells (Galmes et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells

Focosi¹,

Macera

Boggi

et al. 2015

Journal of General Virology

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Torque teno virus (TTV) is increasingly considered a universal marker of global immune function. The virus is supposed to replicate in lymphocytes, but poor information is available about fluctuations of viraemia after administration of anti-lymphocyte agents. We studied TTV kinetics in a cohort of 70 kidney±pancreas recipients receiving one of two different anti-T-cell induction immunosuppressants. During the first 30 days after anti-T-cell antibody administration, we report kinetics of TTV viraemia compatible with replication in T lymphocytes, and highly dependent on the potency of the anti-T-cell drug administered.

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“…Infact, they were positively correlated at all sampling ages except for the detection rate of TTSuV1 at 150 days of age which was negatively correlated. In humans, PBMCs and bone marrow hematopoitic cells have been suggested as the two possible sites of TTV replication [11,12,31]. However, it is unknown whether the detection of TTSuVs in PBMC in our study corresponds to the virus tropism to PBMC.…”

Section: Ttsuv2mentioning

confidence: 74%

Infection Dynamics of Torque Teno Sus Virus Types 1 and 2 in Serum and Peripheral Blood Mononuclear Cells

Tshering

Takagi

Deguchi

2012

The Journal of Veterinary Medical Science

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ABSTRACT. This study was carried out to investigate the presence of Torque teno sus virus types 1 (TTSuV1) and 2 (TTSuV2) in a longitudinally (14 to 150 days of age) collected paired pooled sera (pSE) and peripheral blood mononuclear cells (pPBMCs) using nested polymerase chain reaction. The detection rate of TTSuV1 in pSE increased from 14 to 90 days of age, but a progressive decline was observed from 120 to 150 days of age, while in pPBMC, a high value was maintained till the end of growing-finishing period. On the contrary, except in PBMCs at 30 days of age, high detection rates of TTSuV2 were found in both pSE and pPBMCs in all sampling ages. The detection rate of TTSuVs between pSE and pPBMCs was positively correlated at all sampling ages except for TTSuV1 at 150 days of age. This is the first study showing the presence of TTSuVs in PBMCs from pigs and describing the in vivo infection dynamics of TTSuV in paired sera and PBMCs during the entire growing and finishing periods of pigs reared in conventional farms.

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TT virus (TTV) loads associated with different peripheral blood cell types and evidence for TTV replication in activated mononuclear cells

Cited by 103 publications

References 27 publications

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Short-term kinetics of torque teno virus viraemia after induction immunosuppression confirm T lymphocytes as the main replication-competent cells

Infection Dynamics of <i>Torque Teno Sus Virus</i> Types <i>1</i> and <i>2</i> in Serum and Peripheral Blood Mononuclear Cells

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