Prevalence of the Novel Torque Teno Sus Virus Species k2b from Pigs in the United States and Lack of Association with Post-Weaning Multisystemic Wasting Syndrome or Mulberry Heart Disease.

The family Anelloviridae includes a number of viruses infecting humans (Torque teno viruses, TTV) and other animals including swine (Torque teno sus viruses, TTSuV). Two genetically distinct TTSuV species have been identified from swine thus far (TTSuV1 and TTSuVk2), although their definitive association with disease remains debatable. In 2012, a novel TTSuV species was identified from commercial swine serum and classified in the genus Kappatorquevirus as TTSuVk2b. The other Kappatorquevirus species, TTSuVk2a, has been associated with post-weaning multisystemic wasting syndrome (PMWS) when coinfected with porcine circovirus type 2 (PCV2). Therefore, in this study, we initially amplified a portion of TTSuVk2b ORF1 and, subsequently, assessed the molecular prevalence of the virus in pigs in the United States. A total of 127 serum and 115 tissue samples were obtained from pigs with PMWS or mulberry heart disease (MHD) in six states and tested by PCR for the presence of TTSuVk2b DNA. Approximately 27.6% of the serum and 21.7% of tissue samples tested positive for TTSuVk2b DNA, and the positive products were confirmed by sequencing. However, we did not detect a correlation between TTSuVk2b infection and PMWS or MHD. The near full-length genomic sequence of US TTSuVk2b was determined, and sequence analysis revealed that the US TTSuVk2b isolates were 95% identical to the TTSuVk2b isolate from Spain, with most of the variations clustering in ORF1. We conclude that the novel TTSuVk2b species is present in pigs in the United States and its potential association with a disease warrants further investigation.

Higher pre-infection vitamin E levels are associated with higher mortality in HIV-1-infected Kenyan women: a prospective study.

BACKGROUND: Low vitamin E levels are often found in HIV-1 infection, and studies have suggested that higher levels may decrease the risk of disease progression. However, vitamin E supplementation has also been reported to increase CCR5 expression, which could increase HIV-1 replication. We hypothesized that vitamin E levels at HIV-1 acquisition may influence disease progression. METHODS: Vitamin E status was measured in stored samples from the last pre-infection visit for 67 Kenyan women with reliably estimated dates of HIV-1 acquisition. Regression analyses were used to estimate associations between pre-infection vitamin E and plasma viral load, time to CD4 count <200 cells/muL, and mortality. RESULTS: After controlling for potential confounding factors, each 1 mg/L increase in pre-infection vitamin E was associated with 0.08 log10 copies/mL (95% CI -0.01 to +0.17) higher set point viral load and 1.58-fold higher risk of mortality (95% CI 1.15-2.16). The association between higher pre-infection vitamin E and mortality persisted after adjustment for set point viral load (HR 1.55, 95% CI 1.13-2.13). CONCLUSION: Higher pre-infection vitamin E levels were associated with increased mortality. Further research is needed to elucidate the role vitamin E plays in HIV-1 pathogenesis.

Benign coxsackievirus damages heart muscle in iron-loaded vitamin E-deficient mice.

Several oxidative stressors (dietary selenium deficiency, dietary vitamin E deficiency coupled with fish oil feeding, genetic reduction of glutathione peroxidase activity) allow a normally benign coxsackievirus B3 (CVB3/0) to damage heart muscle in host mice. This study investigated whether dietary iron overload, another oxidant stress, would also permit CVB3/0 to exert a cardiopathologic effect in vitamin E-deficient (-VE) mice. Four groups of mice were fed either a -VE or a +VE diet containing either an adequate or an excessive (30x) amount of iron. After 4 weeks of feeding, the mice were inoculated with CVB3/0 and heart damage was assessed at various times postinfection. Mice fed a diet sufficient in VE with excess iron developed heart damage equivalent to mice fed a diet deficient in vitamin E without excess iron. However, severe heart damage occurred in the group fed a diet deficient in VE with excess iron, which was the most pro-oxidative diet. The highest heart viral titers were found in mice fed the -VE/excessive iron diet. However, the extent of heart damage did not always correlate with the formation of TBARS in liver homogenates. Further research is needed to clarify the role of oxidative stress and iron overload in determining the course of viral infection.

Selenium and viral virulence.

A mouse model of coxsackievirus-induced myocarditis is being used to investigate nutritional determinants of viral virulence. This approach was suggested by research carried out in China which showed that mice fed diets composed of low selenium ingredients from a Keshan disease area suffered more extensive heart damage when infected with a coxsackie B4 virus than infected mice fed the same diet but supplemented with selenium by esophageal intubation. Selenium deficiency in our mice increased the virulence of an already virulent strain of coxsackievirus B3 (CVB3/20) and also allowed conversion of a non-virulent strain (CVB3/0) to virulence. Such conversion of CVB3/0 was accompanied by a change in the viral genome to more closely match that of the virulent virus, CVB3/20. As far as the authors are aware, this is the first report of host nutrition influencing the genetic make-up of an invading pathogen. Nutritionists may need to consider this mechanism of increased viral virulence in order to gain a better understanding of diet/infection relationships.

Selected vitamins in HIV infection: a review.

In this article we review published studies on the role of serum micronutrient levels in the natural history of HIV infection. Specifically, we have focused on vitamins B12, E, A, and beta-carotene. Deficiencies of one or several of these vitamins have been associated with an accelerated progression of HIV infection to AIDS. Most investigators have used serum micronutrient levels as an indicator of vitamin nutriture. However, serum levels are not always the most sensitive or specific indicators of vitamin status. Nonetheless, serum vitamin levels are relatively easy to obtain and have been studied in various HIV-infected populations in individuals at different stages of disease. Low serum B12 levels have been associated with increased neurologic abnormalities, more rapid HIV disease progression, and increased AZT-related bone marrow toxicity. Low serum vitamin E levels have been associated with an increase in oxidative stress in HIV-infected individuals. However, early studies of vitamin E supplementation suggest that vitamin E may have important immunostimulatory properties. Studies of vitamin A deficiency in HIV-infected populations have shown that low serum vitamin A levels are associated with increased mortality, more rapid disease progression, and increased maternal-fetal transmission. However, there is little evidence that vitamin A supplementation, beyond the correction of deficiency, is beneficial in HIV infection. Finally, several clinical trials of beta-carotene supplementation have failed to show significant or sustained improvements in the immune response of patients with HIV infection or AIDS.

Increased virulence of coxsackievirus B3 in mice due to vitamin E or selenium deficiency.

Nutrition has long been known to affect the ability of the host to respond to infectious disease. Widespread famines are often accompanied by increased morbidity and mortality due to infectious diseases. The currently accepted view of the relationship between nutrition of the host and its susceptibility to infectious disease is one of a direct relationship with host immune status. That is, if the nutritional status of the host is poor-due to either single or multiple nutrient deficiencies-then the functioning of the host immune system is compromised. This impairment of the immune response will lead to an increased susceptibility to infectious disease. Clearly, the immune response has been shown to be weakened by inadequate nutrition in many model systems and in human studies. However, what about the effect of host nutrition on the pathogen itself? Our laboratory has shown, using a mouse model of coxsackievirus-induced myocarditis, that a host deficiency in either selenium or vitamin E leads to a change in viral phenotype, such that an avirulent strain of the virus becomes virulent and a virulent strain becomes more virulent. The change in phenotype was shown to be due to point mutations in the viral genome. Once the mutations occur, the phenotype change is stable and can now be expressed even in mice of normal nutriture. Our results suggest that nutrition can affect not only the host, but the pathogen as well, and demonstrate a new model of relating host nutritional effects to viral pathogenesis.