Human Torque teno virus: epidemiology, cell biology and immunology

Torque teno virus (TTV) was discovered in 1997 in the serum of a Japanese patient who had a post-transfusion hepatitis of unknown etiology. It is a small virus containing a circular single-stranded DNA genome which is unique among human viruses. Within a few years after its discovery, the TTVs were noted to form a large family of viruses with numerous genotypes. TTV is highly prevalent among the general population throughout the world, and persistent infections and co-infections with several genotypes occur frequently. However, the pathogenicity and the mechanism for the sustained occurrence of the virus in blood are at present unclear. To determine the prevalence of TTV in Finland, we set up PCR methods and examined the sera of asymptomatic subjects for the presence of TTV DNA and for genotype-6 DNA. TTV was found to be highly prevalent also in Finland; 85% of adults harbored TTV in their blood, and 4% were infected with genotype-6. In addition, TTV DNA was detected in a number of different tissues, with no tissue-type or symptom specificity. Most cell-biological events during TTV infections are at the moment unknown. Replicating TTV DNA has, however, been detected in liver and the hematopoietic compartment, and three mRNAs are known to be generated. To characterize TTV cell biology in more detail, we cloned in full length the genome of TTV genotype 6. We showed that in human kidney-derived cells TTV produces altogether six proteins with distinct subcellular localizations. TTV mRNA transcription was detected in all cell lines transfected with the full-length clone, and TTV DNA replicated in several of them, including those of erythroid, kidney, and hepatic origin. Furthermore, the viral DNA replication was shown to utilize the cellular DNA polymerases. Diagnoses of TTV infections have been based almost solely on PCR, whereas serological tests, measuring antibody responses, would give more information on many aspects of these infections. To investigate the TTV immunology in more detail, we produced all six TTV proteins for use as antigens in serological tests. We detected in human sera IgM and IgG antibodies to occur simultaneously with TTV DNA, and observed appearance of TTV DNA regardless of pre-existing antibodies, and disappearance of TTV DNA after antibody appearance. The genotype-6 nucleotide sequence remained stable for years within the infected subjects, suggesting that some mechanism other than mutations is used by this minute virus to evade our immune system and to establish chronic infections in immunocompetent subjects.

Evaluation of Mycoplasma hyopneumoniae bacterins for porcine torque teno virus DNAs

Objective-TO determine whether commercial Mycoplasma hyopneumoniae bacterins sold for use in swine contain porcine torque teno virus (TTV).

Effect of coinfection with genogroup 1 porcine torque teno virus on porcine circovirus type 2-associated postweaning multisystemic wasting syndrome in gnotobiotic pigs

Objective—To determine whether genogroup 1 porcine torque teno virus (g1-TTV) can potentiate clinical disease associated with porcine circovirus type 2 (PCV2).

Sample population—33 gnotobiotic baby pigs.

Procedures—Pigs were allocated into 7 groups: group A, 5 uninoculated control pigs from 3 litters; group B, 4 pigs oronasally inoculated with PCV2 alone; group C, 4 pigs inoculated IP with first-passage g1-TTV alone; group D, 4 pigs inoculated IP with fourth-passage g1-TTV alone; group E, 6 pigs inoculated IP with first-passage g1-TTV and then oronasally inoculated with PCV2 7 days later; group F, 6 pigs inoculated IP with fourth-passage g1-TTV and then inoculated oronasally with PCV2 7 days later; and group G, 4 pigs inoculated oro-nasally with PCV2 and then inoculated IP with fourth-passage g1-TTV 7 days later.

Results—6 of 12 pigs inoculated with g1-TTV prior to PCV2 developed acute onset of postweaning multisystemic wasting syndrome (PMWS). None of the pigs inoculated with g1-TTV alone or PCV2 alone or that were challenge exposed to g1-TTV after establishment of infection with PCV2 developed clinical illness. Uninoculated control pigs remained healthy.

Conclusions and Clinical Relevance—These data implicated g1-TTV as another viral infection that facilitates PCV2-induced PMWS. This raises the possibility that torque teno viruses in swine may contribute to disease expression currently associated with only a single infectious agent.

Preliminary study of Porcine circovirus type 2 and Torque teno sus virus coinfection frequencies in Brazilian pig herds

Torque teno sus virus (TTSuV) is emergent in swine herds. Recent studies have shown an increased frequency of TTSuV2 in Porcine circovirus type 2 (PCV2)-associated diseases (PCVAD), which are endemic in many swine-producing countries, including Brazil. Coinfection with several other viral and bacterial agents results in an increased incidence of more severe PCVAD. Given the limited information on TTSuV and PCV2 coinfection, especially in Brazilian swine herds, this study made a preliminary estimation of the occurrence of coinfection in swine herds by testing samples from different categories. Between 2008 and 2009, 111 samples of feces and 23 serum samples from 5 swine herds were tested for PCV2 and TTSuVs and the results analyzed for associations between these agents. No significant differences in coinfection frequency were observed for PCV2 1 + TTSuV1 or for PCV2 1 TTSuV2 between nursery piglets (P = 0.730), growing pigs (P = 0.331), or sows (P = 0.472). However, a significant difference was observed for PCV2 1 TTSuV1 1 TTSuV2 between nursery piglets and growing pigs (P = 0.004; Fisher's exact test). Phylogenetic studies agreed with the grouping of TTSuV1 and TTSuV2 into 2 different clades, with no distinct pattern of clustering of these isolates with the animal categories.

Genetic diversity of Atlantic salmon (Salmo salar) and European whitefish (Coregonus lavaretus) in the Baltic Sea

We described the patterns and extent of microsatellite DNA variation in historical and present-day Atlantic salmon (Salmo salar L.) stocks in the Baltic Sea and neighbouring areas, and in European whitefish (Coregonus lavaretus) ecotypes, populations and run-timing types in Finland. Moreover, the amount and pattern of genetic diversity in historical salmon populations before human impact were described, and the proportion of diversity maintained in the present hatchery stocks evaluated. Salmon populations in the Baltic Sea were, on average, significantly less variable than eastern Atlantic populations, and the diversity of landlocked populations (Lakes Vänern, Saimaa, Onega and Ladoga) was in turn significantly lower than that of anadromous salmon populations in the Baltic Sea populations. Within the Baltic Sea, the anadromous populations of Atlantic salmon formed three clear groups, corresponding to the northern (Gulf of Bothnia), eastern (Gulf of Finland and eastern Baltic Main Basin) and southern (western Baltic Main Basin) regions. Based on microsatellite data, three salmon population groups in the Baltic Sea were considered potentially different colonization lineages. In short- and long-term breeding programmes of Atlantic salmon, the average observed rate of loss of alleles was 4.9% and 2.0% per generation and the average rate of loss of heterozygosity was 1.4% and 1% per generation, respectively. When comparing the genetic parameters of stocks before and after hatchery breeding of several successive generations (Rivers Iijoki and Oulujoki), statistically significant changes in allele frequencies were common, while large wild stock in the Teno River has remained temporally very stable over 56 years. Despite the observed losses of genetic diversity in broodstock breeding, a large proportion of the genetic resources of the extirpated stocks are still conserved in the broodstocks. Genetic differentiation among European whitefish ecotypes was generally low, thus giving support to the hypothesis of one native European whitefish species in Fennoscandia. Among the ecotypes, the northern, large sparsely rakered, bottom-dwelling whitefish was the most unique. The known genetic differences in quantitative traits have thus either developed independently of potential phylogenetic lineages, or the lineages have mixed and the quantitative traits of the ecotypes, like gill-raker number, have later changed according to environment and selection pressures. Overall, genetic distances between the anadromous whitefish populations along the Finnish coast, especially in the Bothnian Bay area, were small. Wild whitefish populations studied had slightly higher allelic diversity than hatchery-reared populations in corresponding rivers.

Intercultural leadership and negotiation

This project will examine cultural differences and dimensions and how they affect negotiations and intercultural management. It is necessary to consider that the cultural characteristics of each society, which in turn is made of different individuals, make intercultural relations complex and with many subtleties. We will apply these proposals to draw a comparison between Spain and two Southeast Asian countries: India and Sri Lanka using Hofstede’s cultural dimensions.This project will examine cultural differences and dimensions and how they affect negotiations and intercultural management. It is necessary to consider that the cultural characteristics of each society, which in turn is made of different individuals, make intercultural relations complex and with many subtleties. We will apply these proposals to draw a comparison between Spain and two Southeast Asian countries: India and Sri Lanka using Hofstede’s cultural dimensions.