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PubMed2001

Case-control studies on host factors in severe malaria.

Although molecular biology has illustrated the phenotypic heterogeneity of Plasmodium falciparum, there are still no specific markers of virulence. As parasite virulence is an important determinant of severe malaria, the choice of comparison groups in the study of host factors influencing severity is a delicate issue. Ignoring parasite factors in the selection of controls potentially leads to biased comparisons between a majority of cases with virulent parasites and a majority of controls with non-virulent parasites. This article discusses how to avoid this virulence bias in the absence of specific markers of virulence.

Animals↗
PubMed2002

Membrane heme as a host factor in reducing effectiveness of dihydroartemisinin.

Plasmodium falciparum infecting alpha-thalassemic erythrocytes are resistant to artemisinin and its derivatives. Binding of the drug to hemoglobin H resulting in drug inactivation was previously demonstrated. We now show that an additional host factor, membrane heme, significantly accounted for decreased antimalarial activity of artemisinin. The antimalarial activity of dihydroartemisinin in the presence of normal and thalassemic erythrocyte membranes showed a correlation with the heme content of the membrane (r(2)=0.466, P<0.01). The correlation was more clearly seen when the drug effectiveness was correlated with the heme content of alpha-thalassemic membrane (r(2)=0.636, P<0.01). However, the drug effectiveness showed no correlation to ferrozine-reactive (free or non-heme) iron content (r(2)=0.0001, P>0.05). alpha-Thalassemic erythrocytes contained higher amounts of membrane heme (11.04+/-8.96 nmol/mg membrane protein) than those from normal and beta-thalassemia/HbE erythrocytes (2.68+/-1.28 and 3.98+/-3.98 nmol/mg membrane protein, respectively, P<0.01). Loss of drug effectiveness was also correlated with increment of heme content in membrane prepared from normal erythrocytes treated with phenylhydrazine. It is concluded that heme in both normal and thalassemic erythrocyte membranes is an important factor in drug inactivation.

Artemisinins↗
PubMed2005

The interaction of HIV-1 with the host factors.

Human immunodeficiency virus type 1 (HIV-1) is a causative agent of acquired immunodeficiency syndrome (AIDS) in humans. In the last decade, the functions of HIV-1-encoded genes have been intensively studied. These studies have contributed to the development of the effective anti-AIDS drugs directing against the HIV-1-encoded enzymes, namely reverse transcriptase and protease. However, even the combination of these drugs is not sufficient enough to stop the progression of AIDS partly due to the emergence of drug-resistant HIV-1 mutants as well as the severe side effects. Understanding the molecular mechanisms by which cellular factors support the efficient replication of HIV-1 should contribute to develop means to control the progression of AIDS. This field is now expanding rapidly. Here we review the host factors involved in the replication of HIV-1 and highlight some findings that have a substantial impact on the retroviral research.

HIV Infections↗
PubMed2001

The effect of host factors and capsule composition on the cellular overgrowth on implanted alginate capsules.

Microencapsulation of islets of Langerhans in alginate/poly-L-lysine (PLL)/alginate capsules may provide a method for transplantation in the absence of immunosuppression. The aim of this study was to investigate the problem of overgrowth on implanted capsules with regard to the composition of the capsules and host factors such as cytokine and nitric oxide production. Empty capsules were implanted to C57BL/6 mice for 1, 3, 7, or 28 days. Glucose oxidation rates showed the metabolic activity of the cellular overgrowth on retrieved capsules. DNA content, histological score, and retrieval rates were also measured to assess the overgrowth. It was noted that the pericapsular host reaction arose by day 7 and had not increased further by day 28. Capsules of varying alginate compositions and different concentrations of PLL were implanted for 7 days to either C57BL/6 or Balb/c mice. Capsules were also implanted to mice lacking the inducible nitric oxide synthase enzyme. Glucose oxidation rates, DNA content, and histological score were positively correlated to each other and negatively correlated to retrieval rates. The pericapsular reaction was reduced if PLL was omitted from the capsule or if a high mannuronic acid alginate was used. Balb/c mice had reduced cellular overgrowth on implanted capsules and had reduced mRNA expression of interleukin-1 beta and tumor necrosis factor-alpha in their peritoneal macrophages. The capsular overgrowth seemed more severe in animals lacking inducible nitric oxide synthase compared with wild-type controls. It is concluded that alginate composition, PLL, and recipient factors such as nitric oxide production and cytokine expression affect the cellular overgrowth on implanted alginate capsules.

Alginates↗
PubMed1995

Prevalence of asymptomatic bacteriuria and associated host factors in women with diabetes mellitus. The Manitoba Diabetic Urinary Infection Study Group.

A prospective study was undertaken to determine the prevalence of significant asymptomatic bacteriuria in adult women with diabetes mellitus attending endocrinology clinics at two tertiary-care university-affiliated teaching hospitals. In addition, host factors of the patients were correlated with bacteriuria. The overall prevalence of bacteriuria was 7.9% (85 cases per 1,072 women). Absolute urinary leukocyte (white blood cell) counts were > or = 10/mm3 in 77.6% (66) of the 85 bacteriuric women vs. 23.7% (234) of the 987 nonbacteriuric women (P < .001). Bacteriuric women were significantly more likely than nonbacteriuric women to have non-insulin-dependent diabetes mellitus, longer duration of diabetes, neuropathy, and heart disease. Aboriginals had bacteriuria at a significantly higher prevalence rate than that among nonaboriginals (19.7% [15 of 76] vs. 7.0% [70 of 996], respectively; P < .0001), were more likely to have occult upper urinary tract infection (antibody-coated bacteria positivity: 53% [8 of 15] vs. 20% [10 of 50], respectively; P = .016), and had significantly lower urinary leukocyte counts, whether they were bacteriuric or not (P < .05). Multivariate analysis identified duration of diabetes and aboriginal origin as independent risk factors for the presence of bacteriuria.

Adolescent↗
PubMed1994

Host factors affecting seroprevalence of bluetongue virus infections of cattle.

Results of testing of 19,731 samples from a serologic survey of cattle with bluetongue virus (BTV) infections in Australia were analyzed for association between age, species, or sex and test result. Bivariate analysis indicated that all 3 host factors were associated with test result. After adjusting for confounding caused by the location of each animal in the study (high, moderate, and low BTV prevalence regions), cattle > or = 4 years old had an odds ratio of 4.33 (95% confidence interval, 3.99, 4.71) for a positive test result, compared with that for cattle < 2 years old. Cattle 2 to 4 years had an odds ratio of 2.28 (2.14, 2.54), compared with cattle < 2 years old. Bos taurus cattle had an odds ratio of 1.76 (1.63, 2.05) of a positive test result, compared with crossbred cattle, and B indicus cattle had an odds ratio of 1.20 (1.09, 1.33), compared with crossbred cattle. Sexually intact (+) male cattle were found to have an odds ratio of 3.13 (2.66, 3.49) for a positive test result, compared with castrated male (-) cattle, and female cattle were found to have an odds ratio of 1.38 (1.29, 1.48), compared with male (-) cattle. Multivariate analysis of BTV testing results was performed, using stepwise logistic regression. The most parsimonious model selected included age, species, and sex factors, and first-order interaction terms between these factors. This model was only able to be fit to data from cattle restricted to the high (> 25%) BTV prevalence region. Odds ratio were found to increase with age for male (-) cattle of all species.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

The integration host factor stimulates interaction of RNA polymerase with NIFA, the transcriptional activator for nitrogen fixation operons.

The regulatory protein NIFA activates transcription of nitrogen fixation (nif) operons by the sigma 54 holoenzyme form of RNA polymerase. NIFA from Klebsiella pneumoniae activates transcription from the nifH promoter in vitro; in addition, the integration host factor, IHF, binds between the nifH promoter and an upstream binding site for NIFA. We demonstrate here that IHF greatly stimulates NIFA-mediated activation of nifH transcription in vitro and thus that the two factors are functionally synergistic. Electron micrographs indicate that IHF bends the DNA in the nifH promoter regulatory region. Although IHF binds close to the nifH promoter, it does not directly stimulate binding of sigma 54 holoenzyme. Rather, the IHF-induced bend may facilitate productive contacts between NIFA and sigma 54 holoenzyme that lead to the formation of open complexes. IHF binds to nif promoter regulatory regions from a variety of organisms within the phylum "purple bacteria," suggesting a general ability to stimulate NIFA-mediated activation of nif transcription.

Bacterial Proteins↗
PubMed1977

Viral attributes and host factors in carcinogenesis: herpesviruses.

This paper describes two different experiments of nature: 1) the persistence of unusual virus strains of Epstein-Barr virus (EBV) (which proved oncogenic in vitro) and cytomegalovirus (CMV) in lymphoid cells following congenital or early acquired infection; 2) the occurence of multiple cases of Burkitt's lymphoma and nasopharyngeal carcinoma in one family. All the members of this family were EBV viral capsid antigen (VCA) and nuclear antigen (EBNA) antibody positive. The two patients with nasopharyngeal carcinoma had high titers of EBV-VCA, EA, and EBNA antibodies. The only member of this family having EBV early antigen (EA antibodies in addition to the patients with tumors was the mother. Borderline IgA deficiency was documented in 3 members of this family. These findings illustrate the importance of host factors (intracellular resistance to transformation and secondarily, immunological surveillance) in the outcome of the host-virus challenge whether cancer or infectious disease is the outcome. Extensive studies of these cases may provide the best insight into the mysteries of viral oncogenesis.

Antibodies, Viral↗
PubMed1995

The Holliday junction intermediates of lambda integrative and excisive recombination respond differently to the bending proteins integration host factor and excisionase.

In lambda site-specific recombination, the integrative and excisive reactions proceed via two different Holliday junction intermediates, both of which are generated and resolved by a pair of sequentially ordered single strand exchanges. Factors affecting the directionality and efficiency of the second pair of strand exchanges were examined using artificial Holliday junctions (chi-forms). The integrative and excisive recombination intermediates respond differently to the accessory DNA bending proteins integration host factor and excisionase (Xis). These differences between the two recombination intermediates result from a different interaction pattern between proteins binding to the left (P arm) and right (P' arm) of the crossover region. The effect of Xis protein on the directionality of resolution, i.e. the choice of which strands are exchanged, is consistent with a role in promoting the second strand exchange during excision. Proteins binding to the left of the crossover region (P arm) primarily influence the directionality of resolution, while proteins binding to the right (P' arm) have a greater effect on the overall efficiency of resolution. Together, the effect of proteins binding to sites in the P and P' arms is to greatly enhance resolution of the two different Holliday intermediates and to favor resolution in the 'forward' direction for both integrative and excisive recombination.

Bacteriophage lambda↗
PubMed2025

Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA.

While SARS-CoV-2 vaccines have shown strong efficacy, the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19, especially in locations with suboptimal vaccination uptake. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within the prior 3-9 months was associated with decreased odds of moderate disease, severe disease, and death. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.

Humans↗
PubMed1997

Interferon therapy in HCV-positive mixed cryoglobulinaemia: viral and host factors contributing to efficacy of the therapy.

BACKGROUND: In a previous paper, we reported on the short-term efficacy of alpha-interferon in the treatment of hepatitis C virus positive mixed cryoglobulinaemia. AIMS: We investigated the long-term effects of therapy in a larger group of patients, and the viral and host factors able to influence the response to treatment. METHODS: In 27 females and 15 males (mean age 54.8 +/- 9.1 years) affected by mixed cryoglobulinaemia, bone marrow biopsy and phenotyping of marrow cells were performed before treatment and at the end of follow-up. A liver biopsy was obtained from patients showing biochemical signs of chronic liver disease. The presence of hepatitis C virus was assessed by detection of serum anti-hepatitis C virus antibodies, and hepatitis C virus-RNA. The treatment schedule was 3 million units of recombinant interferon alpha-2b three times a week for one year. Follow-up lasted for 1 year after the end of treatment. The response was classified as follows: 1) Complete response: Disappearance of the cryocrit (or reduction of more than 50%) and of all clinical manifestations of the disease. 2) Partial response: Disappearance of all clinical signs of the disease, but reduction of cryocrit of less than 50%. 3) Minor response: Reduction of cryocrit of less than 20% associated with the disappearance of one or more (but not all) signs of vasculitis. RESULTS: Anti-hepatitis C virus antibodies were present in 41 (95%) patients, and hepatitis C virus-RNA was detectable in all cases. Before therapy, marrow histology showed a massive monomorphous infiltration by plasmacytoid lymphocytes indicating the presence of low-grade non-Hodgkin lymphoma in 7 cases (16.6%). After therapy, 13 (31%) patients achieved a complete response, 23 patients (55%) a partial response, and 6 patients (14%) a minor response. Seven of the responders and all patients showing partial or minor responses relapsed a few months after withdrawal of therapy. At the end of the follow-up, only 6 patients had obtained complete remission. Bone marrow examination showed that B-lymphocytic monoclonal infiltrate had disappeared in 3 long-term responders. No difference was found between responders and non-responders/relapsers in terms of age, sex, duration of the disease, severity of symptoms, liver function tests, rheumatoid factor or complement levels, while the lack of response was associated with the presence of genotype 1b, liver cirrhosis, and high cryoglobulin level. CONCLUSIONS: Mixed cryoglobulinaemia is associated with a high prevalence of B-cell lymphomas. Alpha-Interferon is an effective agent for the treatment of this disease and seems able to determine regression of the lymphoproliferative disorder. The hepatitis C virus genotype and cryoglobulin level are the most important predictive factors of response to therapy.

Antiviral Agents↗
PubMed1985

The phi 80 and P22 attachment sites. Primary structure and interaction with Escherichia coli integration host factor.

Although the lambdoid bacteriophage phi 80 and P22 possess site-specific recombination systems analogous to bacteriophage lambda, they have different attachment (att) site specificities. We have identified and determined the nucleotide sequences of the att sites of phi 80 and P22 and have examined the interaction of these sites with purified Escherichia coli integration host factor (IHF). The sizes of the homologous core regions of the att sites vary greatly: P22 has a 46-base pair core, while phi 80 and lambda have 17- and 15-base pair cores, respectively. The core sequences of the three phage show no significant homology, although dispersed regions of homology in arm sequences indicate that the three phage att sites are related. All three att sites have a high A + T composition, and restriction fragments carrying these sites migrate anomalously upon polyacrylamide gel electrophoresis. IHF binds to a site to the left of the common core in the phi 80 and P22 phage att sites (attP) and to a site to the right of the core in P22 attP and attB (the bacterial att site). In the lambda system, IHF interacts with three regions on attP (designated H1, H2, and H') and none on attB (Craig N., and Nash, H.A. (1984) Cell 39, 707-716). Alignment of the IHF sites of all three phage results in a consensus sequence for IHF binding, Pyr-AANNNNTTGATAT. Among the three phage, the number of IHF sites differs; however, the location and orientation of the binding sites in relation to the respective core regions are well conserved. An IHF site analogous to lambda H2 is present in both phi 80 and P22 attP, while a site analogous to lambda H' is present in P22 attP. This conservation suggests that IHF plays a very similar role in the site-specific recombination pathways of all three phage, and that the flanking arm sequences are necessary for phi 80 and P22 attP function, as is the case for lambda attP function. These structural similarities presumably reflect a conservation of the mechanism of site-specific recombination for the three phage.

Bacteriophage lambda↗
PubMed1990

Host factors in the severity of Q fever.

The author has reviewed different aspects of the role of immunocompetence in the development of Q fever. Coxiella burnetii lives within the phagolysosomes of infected cells. In animals, the immunosuppression caused by either cortisone or X-irradiation reactivates Q fever. In humans, cases of Q fever are reported in immunocompromised hosts suffering from leukemia, cancer, and human immunodeficiency virus infection (AIDS). Similar data are reported with strict or facultative intracellular parasites living within the phagolysosome. Sporadic publications reported the appearance of auto-antibodies during Q fever which may change the clinical picture of the disease. The pathological findings of hepatitis diagnosed during acute Q fever and those with C. burnetii chronic endocarditis are quite different and may reflect a different immunological response to C. burnetii. These facts emphasize the importance of host factors in the clinical expression and outcome of Q fever.

Humans↗
PubMed1992

Use of host factors to identify people at high risk for cutaneous malignant melanoma .

OBJECTIVE: To determine which host characteristics are risk factors for cutaneous malignant melanoma in order to aim prevention and early detection programs at people at high risk. DESIGN: Case-control study. SETTING: Southern Ontario. SUBJECTS: The 583 case subjects were aged 20 to 69 years and had had malignant melanoma newly diagnosed between Oct. 1, 1984, and Sept. 30, 1986. The 608 control subjects were randomly selected from a list of residents in the study area and were stratum matched for age, sex and municipality. INTERVENTION: Through in-person interviews the interviewer ascertained exposure to putative external risk factors and assessed skin colour and number of nevi on the arm, and the subject reported his or her natural hair colour at age 20 years, eye colour, skin reaction to repeated sun exposure, and freckle and whole-body nevus densities. RESULTS: Although all the host factors mentioned were significantly associated with melanoma risk when considered separately, only hair colour, skin reaction to repeated sun exposure, and self-reported freckle and nevus densities remained significant after backward logistic regression analysis. The odds ratio for melanoma was estimated to be 10.7 in people who had many nevi compared with those who had none (95% confidence interval [CI] 6.6 to 17.4), 4.0 in people who had red hair compared with those who had black hair (95% CI 1.9 to 8.2), 1.9 in people who had many freckles compared with those who had none or few (95% CI 1.3 to 2.8) and 1.4 respectively in people who burned and had a subsequent increase in tan and those who burned and had no increase in tan after repeated sun exposure compared with those who did not burn [corrected]. CONCLUSIONS: Four risk factors for malignant melanoma have been identified. Prospective evaluation of their predictive value should be done. In the meantime, however, these factors should be used to identify people apparently at high risk for malignant melanoma, who can then be targeted for early detection and prevention programs.

Adult↗
PubMed1994

Regulation of the Yersinia enterocolitica enterotoxin Yst gene. Influence of growth phase, temperature, osmolarity, pH and bacterial host factors.

The chromosome of Yersinia enterocolitica encodes an enterotoxin called Yst. We analysed transcription of chromosomal yst'--luxAB and plasmid-borne yst'--lacZ operon fusions and we observed that regulation of yst expression occurs at transcriptional level. In a wild-type strain, yst was transcribed from at least two major promoters. yst transcription reached a maximum at the entry to the stationary phase and significantly varied in different Y. enterocolitica strains. In some strains, it gradually decreased during the course of our work, suggesting the existence of a mechanism switching the expression of yst to a silent state. Changes in the status of bacterial host factors rather than modifications in the yst gene are responsible for this silencing. Negative regulator YmoA participates in yst silencing and temperature regulation of yst. YmoA was also required for proper growth-phase regulation of yst, although it is not the only factor involved in this regulation. Physico-chemical parameters of the environment play an important role in yst transcription. In usual culture media (e.g. tryptic soy broth), the enterotoxin gene was transcribed only at temperatures below 30 degrees C, which argued against the role of Yst in a prolonged diarrhoea at body temperatures. However, yst transcription could be induced at 37 degrees C by increasing osmolarity and pH to the values normally present in the ileum lumen. This finding reconciles the observations concerning yst expression in a host environment and in bacterial cultures, thus supporting the idea that enterotoxin Yst is a virulence factor of Y. enterocolitica.

Bacterial Toxins↗
PubMed1998

Effects of training, environment, and host factors on the sweating response to exercise.

Because metabolic heat production is proportional to the amount of work performed, the differences in core body temperature (Tcore) of humans exercising at similar absolute exercise intensities are due to differences in their efficiency of heat dissipation. The purpose of this paper is to delineate the effects of training status, heat acclimation, environmental conditions and host factors on the sweating response to exercise. These factors are reviewed in light of their effects on the biophysical enhancement or suppression of sweating, and modifications of the relationship between local sweat rate and Tcore (degrees C). Athletes are advised to optimize those factors that enhance, and eliminate those factors that diminish, the onset and responsiveness of sweating.

Acclimatization↗
PubMed1996

Expression of L protein of vesicular stomatitis virus Indiana serotype from recombinant baculovirus in insect cells: requirement of a host factor(s) for its biological activity in vitro.

The 241-kDa large (L) protein of vesicular stomatitis virus (VSV) Indiana serotype, a multifunctional catalytic subunit of the viral RNA polymerase, has been expressed in Spodoptera frugiperda cells infected with recombinant baculovirus BacPAK6-L containing the L gene under the control of a polyhedrin promoter. The recombinant L protein was biologically active and supported viral mRNA synthesis in vitro. When the expressed L protein was purified by phosphocellulose column chromatography, it eluted in two peaks, one at 0.4 M NaCl (peak I) and the second at 0.75 M NaCl (peak II). The L protein in peak I showed significant transcriptional activity in an in vitro transcription reconstitution experiment, whereas the L protein in peak II was inactive. Interestingly, the addition of cytoplasmic extract from uninfected Sf21 cells to peak II completely restored transcription in vitro, indicating the requirement of a host factor(s) for the activity of the L protein. This factor is relatively heat stable and is dissociable from the recombinant L protein. It is also present in BHK, COS, and HeLa cells in detectable levels. The role of the putative host protein(s) in the activation of the L protein is discussed.

Animals↗