Kegg Pathway: Cholera - Infection

MLO Med Lab Obs. 2008 Jun; 40(6): 20, 22-5, 47
Schofield CB

The cases presented here illustrate potential epidemic or pandemic events that once-silent pathogens portend. Developing countries, where defenses are limited, are primary targets. Of future concern are the developed countries that fail to use rigorous control measures established by the CDC, the WHO, and others to prevent the spread of infectious diseases. International travel has brought changes in demographics and a greater need for surveillance programs to control selective antibiotic resistance. In our first case, the patient's death would likely have been avoided if he had adhered to the CDC-recommended vaccine program. The fact remains that 20% to 60% of U.S. adults, including travelers to endemic areas, have not followed the diphtheria booster-vaccine schedule. Our second case demonstrates the ease of transmission through food and water that contribute to illness from Cholera. The success of intravenous therapy or ORS treatment has reduced the number of deaths by approximately 3 million per year in Asia and Africa. Though development of oral vaccines may be promising, without water and sewage control, waterborne transmission of Cholera is a continuing threat. The panic following our third case was a sample of the pandemonium an outbreak of XDR-TB would create. Lack of access to medical care and lack of funding in developing countries made selection of resistance from MDR- to XDR-TB a predictable event. The Global Plan to Stop TB 2006-2015, initiated to improve on the DOTS strategy to control TB/HIV and MDR-TB cases, targets 2015 for reducing overall prevalence and mortality from TB. Based on the principle that community healthcare is the best prevention, organizations that are dedicated to the control of emerging and re-emerging Infection include the CDC, NIH, IDSA, ATS, and the National Academy of Science's Institute of Medicine, to mention a few. Recently, they have established plans and programs to address problems of communication among scientists and to improve surveillance in the detection and monitoring of dangerous pathogens. The remarkable and ever-changing dynamics of microbial adaptation, however, requires enormous vigilance and financial priorities worldwide. A coordinated effort by both scientists and public-health leaders is needed if the onslaught of infectious threats is to be controlled.

Bull Environ Contam Toxicol. 2008 Jul 15;
Eja ME, Abriba C, Etok CA, Ikpeme EM, Arikpo GE, Enyi-Idoh KH, Ofor UA

The prevalence of Vibrio species in shellfish and their seasonal variability in the Great Kwa River estuary (GKWE) were examined. Results revealed a trimodal peak in Vibrio counts, coinciding with meteorological changes and the hot periods of the year. The estuary was constantly faecally polluted, coupled with high rates of Infection of shellfish by V. parahaemolyticus 42 (13.6%), V. Cholerae non-01 29 (9.4%) and V. alginolyticus 22 (7.1%), thus posing a health risk. The observed seasonal variability and prevalence of Vibrio species Infection are of epidemiological significance, and provide a guide for effective control of associated Cholera epidemics.

Annu Rev Nutr. 2008 Feb 6;
Rosenberg I

This review strives to make some of the contribution of those prefatory predecessors who have addressed the question of how to strike a balance between the concentration needs of the laboratory bench and bedside research, with participation in the marketplace of ideas and policy. I have been privileged to live most of my career, almost four decades, in an era in which nutrition was coming out of the shadows and demanding recognition in the arena of ideas and policies relating to health. If the first half of the 20th century could be referred to as the era of discovery in nutrition, in which all the vitamins were described and characterized, leading to the seminal contribution of nutritional and enzyme/coenzyme biochemists to the creation of the biochemistry enterprise, then the subsequent half century to this date might be seen as the era of translation, not only of medical science to policy, but also nutrition science with discoveries relating nutrition and diet to infectious disease (as described by Nevin Scrimshaw in the volume 27 prefatory chapter) to heart disease, cancer, fetal development, and aging, among others. As a peripatetic physician-scientist finding sea legs in the 1960s as far away as Bangladesh, a country rife with malnutrition and Cholera and diarrheal disease, it was not hard to be drawn quickly to the idea that those observations that we were making in the field, in the laboratory, and at the bedside needed application in real time. More specifically, tending to the patient on an ingenious volume-collecting Cholera cot, which titrated life-saving volume replacement, cried out for understanding of the pathogenesis and etiology of this disease, and also for action to limit its impact and lethality. Even as we were aware that what we were doing in those very early years of the SEATO/NIH Cholera Research Laboratory, now the ICDR/B, smacked somewhat of medical or scientific colonialism in the 1960s, it would have been hard to dispassionately collect information about what was a life-threatening disease of dehydration for an infant with Cholera, or a sight-threatening degree of xerophthalmia in a child with vitamin A deficiency. So we challenged ourselves, often in some frustration, to go beyond documenting and even individual treatment to a more ambitious challenge of understanding and preventing. That was my baptism, and I use the term advisedly, and exposure to important nutritional problems and their relation to Infection and mortality, and it would have a profound effect on subsequent orientation in both science and career. This was all in keeping with the emerging zeitgeist of diet and disease that was represented at the time by the elucidation of the relationship between diet and heart disease or the diet/heart hypothesis. That theme, the imperative to participate in the translation of nutritional science and policy in a targeted way, forms the structure of this narrative as a kind of memoir, which starts with that early career-directing experience and carries a thread of interest in one of the determinants in nutritional anemia in Asia and the tropics, folic acid or folate, all the way to current fascination with the relationship of that and related vitamins to brain function and aging. This narrative refers to some of the places, institutions, and organizations that provided the opportunities to pursue both science and its translation into policy. Expected online publication date for the Annual Review of Nutrition Volume 27 is July 17, 2007. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Infect Immun. 2008 Jun 30;
Larocque RC, Krastins B, Harris JB, Lebrun LM, Parker KC, Chase M, Ryan ET, Qadri F, Sarracino D, Calderwood SB

An effective vaccine for Vibrio Cholerae is not yet available for use in the developing world, where the burden of Cholera disease is highest. Characterizing the proteins that are expressed by V. Cholerae in the human host environment may provide insight into the pathogenesis of Cholera and assist with the development of an improved vaccine. We analyzed the V. Cholerae proteins present in the stools of 32 patients with clinical Cholera. The V. Cholerae outer membrane porin, OmpU, was identified in all of the human stool samples, and many V. Cholerae proteins were repeatedly identified in separate patient samples. The majority of V. Cholerae proteins identified in human stool are involved in protein synthesis and energy metabolism. A number of proteins involved in the pathogenesis of Cholera, including the A and B subunits of Cholera toxin and the toxin-coregulated pilus, were identified in human stool. In a subset of stool specimens, we also assessed which in vivo-expressed V. Cholerae proteins were recognized uniquely by convalescent, as opposed to acute, sera from Cholera patients. We identified a number of these in vivo-expressed proteins as immunogenic during human Infection. To our knowledge, this is the first characterization of the proteome of a pathogenic bacteria recovered from a natural host.

J Virol. 2008 Jun 11;
Pu Y, Zhang X

It has been shown recently that cell entry of mouse hepatitis virus type 2 (MHV-2) is mediated through endocytosis (Qiu et al., 2006, J. Virol. 80:5768-5776). However, the molecular mechanism underlying MHV-2 entry is not known. Here we employed multiple chemical and molecular approaches to determine the molecular pathways for MHV-2 entry. Our results showed that MHV-2 gene expression and infectivity were significantly inhibited when cells were treated with chemical and physiologic blockers of the clathrin-mediated pathway such as chlorpromazine and hypertonic sucrose medium. Furthermore, viral gene expression was significantly inhibited when cells were transfected with an siRNA specific to the clathrin heavy chain. However, these treatments did not affect the infectivity and gene expression of MHV-A59, demonstrating the specificity of the inhibitions. In addition, over-expression of a dominant-negative mutant of caveolin-1 did not have any effect on MHV-2 Infection while it significantly blocked the caveolin-dependent uptake of Cholera toxin subunit B. These results demonstrate that MHV-2 utilizes the clathrin- but not caveolin-mediated endocytic pathway for entry. Interestingly, when the cells were transiently over-expressed with a dominant negative form (DIII) of Eps15, which is thought to be an essential component of the clathrin pathway, viral gene expression and infectivity were unaffected, although DIII expression blocked transferrin uptake and vesicular stomatitis virus Infection that are dependent on clathrin-mediated endocytosis. Thus, MHV-2 entry is mediated through clathrin-dependent but Eps15-independent endocytosis.

BMC Microbiol. 2008; 8: 94
Yamazaki W, Seto K, Taguchi M, Ishibashi M, Inoue K

BACKGROUND: Vibrio Cholerae is widely acknowledged as one of the most important waterborne pathogen causing gastrointestinal disorders. Cholera toxin (CT) is a major virulence determinant of V. Cholerae. Detection of CT-producing V. Cholerae using conventional culture-, biochemical- and immunological-based assays is time-consuming and laborious, requiring more than three days. Thus, we developed a novel and highly specific loop-mediated isothermal amplification (LAMP) assay for the sensitive and rapid detection of Cholera toxin (CT)-producing Vibrio Cholerae. RESULTS: The assay provided markedly more sensitive and rapid detection of CT-producing V. Cholerae strains than conventional biochemical and PCR assays. The assay correctly identified 34 CT-producing V. Cholerae strains, but did not detect 13 CT non-producing V. Cholerae and 53 non-V. Cholerae strains. Sensitivity of the LAMP assay for direct detection of CT-producing V. Cholerae in spiked human feces was 7.8 x 102 CFU per g (1.4 CFU per reaction). The sensitivity of the LAMP assay was 10-fold more sensitive than that of the conventional PCR assay. The LAMP assay for detection of CT-producing V. Cholerae required less than 35 min with a single colony on thiosulfate citrate bile salt sucrose (TCBS) agar and 70 min with human feces from the beginning of DNA extraction to final determination. CONCLUSION: The LAMP assay is a sensitive, rapid and simple tool for the detection of CT-producing V. Cholerae and will be useful in facilitating the early diagnosis of human V. Cholerae Infection.

Rev Soc Bras Med Trop. 2008 Mar-Apr; 41(2): 179-82
Pereira CS, Amorim SD, Santos AF, Reis CM, Theophilo GN, Rodrigues Ddos P

Aeromonas spp is recognized as pathogenic to humans after consumption of contaminated water and food. In the present investigation, 2,323 rectal swab samples from newborns hospitalized in Rio de Janeiro were evaluated with a view to isolating Aeromonas. The samples were collected and sent to the national reference laboratory for Cholera and other bacterial intestinal Infections, at the Oswaldo Cruz Institute of the Oswaldo Cruz Foundation. The swabs were subjected to enrichment in alkaline peptonated water with the addition of 1% sodium chloride (NaCl) and alkaline peptonated water plus 3% NaCl (37 degrees C/18-24h) and were streaked onto agar that was selective for Pseudomonas-Aeromonas (GSP Agar). Fifty-six Aeromonas strains were isolated, distributed as follows: Aeromonas caviae (42.8%), Aeromonas media (25%), Aeromonas veronii biogroup sobria (10.7%), Aeromonas hydrophila (9%), Aeromonas veronii biogroup veronii (5.3%), Aeromonas sobria (1.8%), Aeromonas jandaei (1.8%), Aeromonas schubertii (1.8%) and Aeromonas sp (1.8%). Resistance to one or more antimicrobial drugs was observed in 26.8% of the strains. Considering the importance of Aeromonas, there is an urgent need to warn about this in relation to nosocomial Infection control.

Future Microbiol. 2008 Jun; 3: 287-98
Cornelissen CN

Gonorrhea is the second most commonly reported infectious disease in the USA, and incidence has been increasing in recent years. Antibiotic resistance among clinical isolates has reached a critical point at which the CDC currently recommends only a single class of antibiotic for treatment. These developments have hastened the search for a vaccine to protect against gonococcal Infections. Vaccine efforts have been thwarted by the ability of the gonococcus to antigenically vary most surface structures. The transferrin-iron transport system is not subject to high-frequency phase or antigenic variation and is expressed by all pathogenic Neisseria. Vaccine formulations comprised of epitopes of the transferrin-binding proteins complexed with inactivated Cholera toxin generated antibodies with potentially protective characteristics. These antigens, and others predicted from genome sequence data, could be developed into a vaccine that protects against neisserial Infections.

Sante Publique. 2008 Jan-Feb; 20(1): 39-57
Guévart E, Ekambi A, Noeske J, Mouangue A, Solle J

Formative supervision is a quality and performance tool based on evaluation and adult training techniques. The 2004 Cholera outbreak in Douala (Cameroon) presented a critical problem in terms of quality of care; formative supervision emerged as the choice of instrument developed as a key response and solution. After a chronological qualitative description of how the supervision team and system were constituted, established and organized, the results are presented: strengthening infrastructure, equipment and organisation; improving the quality of care, hygiene, communication, and management. The system requires capacity building for sustainability in order to also be eventually extended to other health districts and other health sector activities, on the condition that the necessary resources can be mobilized.

Ned Tijdschr Geneeskd. 2008 Apr 5; 152(14): 846; author reply 846
Kerremans JJ

Microb Pathog. 2008 Jul; 45(1): 7-11
Babiuk S, Asper DJ, Rogan D, Mutwiri GK, Potter AA

Type III secreted proteins from Escherichia coli O157:H7 are involved in the attachment of the organism to mammalian cells and have been shown to be effective vaccine components capable of reducing colonization of cattle by the organism. In the current study, we used a streptomycin-treated mouse model to evaluate the efficacy of subcutaneous vs intranasal administration of the vaccine. Following immunization, mice were infected with E. coli O157:H7 and feces were monitored for shedding. Immune responses against EspA and Tir were also monitored. Subcutaneous immunization of mice with type III secreted proteins induced significant EspA- and Tir-specific serum IgG antibodies but did not significantly induce any antigen-specific IgA in feces, whereas intranasal immunization elicited significant EspA- and Tir-specific serum IgG antibodies with some animals developing antigen-specific IgA in feces. Only mice that were immunized intranasally with formulations containing mucosal adjuvants, either Cholera toxin or CpG-containing oligonucleotides, showed decreased E. coli O157:H7 shedding following experimental Infection. Mice immunized subcutaneously with type III secreted proteins did not shed E. coli in feces. These results demonstrate the potential for the use of type III secreted proteins in mucosal vaccine formulations to prevent colonization and shedding of E. coli O157:H7.

Curr HIV Res. 2008 May; 6(3): 230-8
Nowroozalizadeh S, Jansson M, Adamsson J, Lindblad M, Fenyö EM, Holmgren J, Harandi AM

Administration of oligodeoxynucleotides (ODNs) containing CpG motifs generates a rapid and potent response of CC-chemokines, known as ligands of the HIV-1 co-receptor CCR5, in the murine female genital tract. The present study explored the potential HIV inhibitory activities of different human CpG prototypes either alone or conjugated to the non-toxic subunit of Cholera toxin (CTB). Results showed that in vitro replication of both HIV-1 and HIV-2 can be suppressed by different human CpG prototypes. Importantly, the conjugation of CpG ODN to CTB (CTB-CpG) enhanced the antiviral activity of CpG against primary HIV-1 isolates of both R5 and X4 phenotypes in peripheral blood mononuclear cells (PBMC) as well as U87.CD4 co-receptor indicator cells. CTB-CpGs triggered higher amounts of MIP-1alpha, and MIP-1beta in PBMC than the corresponding CpG ODNs, which may explain the superior antiviral effect of CTB-CpG against R5 virus in PBMC. Incubation of PBMC with CpG ODN and CTB-CpG did not alter surface expression of HIV-1 receptors indicating that the observed anti-HIV-1 effect is not mediated through down regulation of HIV-1 receptors on target cells. Further, the enhanced antiviral effect of CTB-CpG was dependent on the presence of phosphorothioate backbone in the ODN, whereas the presence of CpG motif in ODNs was dispensable. These results have implications for the development of novel intervention strategies to prevent HIV Infection.

Curr HIV Res. 2008 May; 6(3): 218-29
Matoba N, Griffin TA, Mittman M, Doran JD, Alfsen A, Montefiori DC, Hanson CV, Bomsel M, Mor TS

CTB-MPR(649-684), a translational fusion protein consisting of Cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produced CTB MPR(649-684) was purified to homogeneity by two affinity chromatography steps. Similar to gp41 and derivatives thereof, the MPR domain can specifically and reversibly self-associate. The affinities of the broadly-neutralizing monoclonal Abs 4E10 and 2F5 to CTB MPR(649-684) were equivalent to their nanomolar affinities toward an MPR peptide. The fusion protein's affinity to GM1 ganglioside was comparable to that of native CTB. Rabbits immunized with CTB-MPR(649-684) raised only a modest level of anti-MPR(649-684) Abs. However, a prime-boost immunization with CTB-MPR(649-684) and a second MPR(649-684)-based immunogen elicited a more productive anti-MPR(649-684) antibody response. These Abs strongly blocked the epithelial transcytosis of a primary subtype B HIV-1 isolate in a human tight epithelial model, expanding our previously reported results using a clade D virus. The Abs recognized epitopes at the N-terminal portion of the MPR peptide, away from the 2F5 and 4E10 epitopes and were not effective in neutralizing Infection of CD4+ cells. These results indicate distinct vulnerabilities of two separate interactions of HIV-1 with human cells - Abs against the C-terminal portion of the MPR can neutralize CD4+-dependent Infection, while Abs targeting the MPR's N-terminal portion can effectively block galactosyl ceramide dependent transcytosis. We propose that Abs induced by MPR(649-684)-based immunogens may provide broad protective value independent of Infection neutralization.

Mar Mirror. 2001; 87(4): 460-71
Cook GC

Expert Rev Vaccines. 2008 May; 7(4): 431-5
Chaignat CL, Monti V, Soepardi J, Petersen G, Sorensen E, Narain J, Kieny MP

Humanitarian aid workers regularly encounter the challenge of setting up functioning surveillance systems immediately after a disaster. Detecting potential outbreaks of diseases, such as Cholera, that might arise from disturbed living conditions, displacement and lack of clean water and sanitation is, therefore, extremely difficult. Fears of Cholera outbreaks are often rife in such conditions and the pertinence of using Cholera vaccines, now available on the market, merit attention. The case of Aceh province, Indonesia, following the 2004 tsunami is examined here: the government of Indonesia decided to carry out a mass vaccination campaign using oral Cholera vaccines, a two-dose product that has not been used widely in the particular circumstances of complex emergencies. The preparation and implementation of this campaign faced many hindrances that unfavorably impacted on the time taken to vaccinate the target population and the costs involved. An estimated 69.3% of the target population received immunization. Evidence gathered during the Aceh campaign could be compared with those of a campaign held in another emergency context--Darfur (Sudan). In spite of many dissimilarities, both experiences illustrate the fact that the question of feasibility and relevance of interventions, as well as prioritization of health needs in complex emergencies, remain crucial to alleviate the affected population's suffering in the most efficient way. Following these two campaigns, WHO recommendations on the use of oral Cholera vaccines in complex emergencies were issued in 2006.

Clin Infect Dis. 2008 Apr 1; 46(7): 970-6
Dechet AM, Yu PA, Koram N, Painter J

BACKGROUND: Infections due to Vibrio species cause an estimated 8000 illnesses annually, often through consumption of undercooked seafood. Like foodborne Vibrio Infections, nonfoodborne Vibrio Infections (NFVI) also result in serious illness, but awareness of these Infections is limited. METHODS: We analyzed illnesses occuring during the period 1997-2006 that were reported to the Centers for Disease Control and Prevention's Cholera and Other Vibrio Illness Surveillance system. The diagnosis of NFVI required isolation of Vibrio species from a patient with contact with seawater. RESULTS: Of 4754 Vibrio Infections reported, 1210 (25%) were NFVIs. Vibrio vulnificus Infections were the most common (accounting for 35% of NFVIs), with 72% of V. vulnificus Infections reported from residents of Gulf Coast states. Infections due to V. vulnificus resulted in fever (72% of cases), cellulitis (85%), amputation (10%), and death (17%). V. vulnificus caused 62 NFVI-associated deaths (78%). Recreational activities accounted for 70% of exposures for patients with NFVIs associated with all species. Patients with liver disease were significantly more likely to die as a result of Infection (odds ratio, 7.8; 95% confidence interval, 2.8-21.9). Regardless of pre-existing conditions, patients were more likely to die when hospitalization occurred >2 days after symptom onset (odds ratio, 2.9; 95% confidence interval, 1.8-4.8). CONCLUSION: NFVIs, especially those due to V. vulnificus, demonstrate high morbidity and mortality. Persons with liver disease should be advised of the risks associated with seawater exposure if a wound is already present or is likely to occur. Clinicians should consider Vibrio species as an etiologic agent in Infections occurring in persons with recent seawater exposure, even if the individual was only exposed during recreational marine activities. Immediate antibiotic treatment with aggressive monitoring is advised in suspected cases.

Ann Clin Microbiol Antimicrob. 2008; 7: 10
Phetsouvanh R, Nakatsu M, Arakawa E, Davong V, Vongsouvath M, Lattana O, Moore CE, Nakamura S, Newton PN

BACKGROUND: Human Infections with non-O1, non-O139 V. Cholerae have been described from Laos. Elsewhere, non Cholera-toxin producing, non-O1, non-O139 V. Cholerae have been described from blood cultures and ascitic fluid, although they are exceedingly rare isolates. CASE PRESENTATION: We describe a farmer who died with Vibrio Cholerae O21 bacteremia and peritonitis in Vientiane, Laos, after eating partially cooked apple snails (Pomacea canaliculata) and mussels (Ligumia species). The cultured V. Cholerae were non-motile. PCR detected ompW and toxR gene regions but not the ctxA, ompU, omp K and TCP gene regions. Although the organisms lacked flagellae on scanning electron microscopy, they possessed the Vibrio flagellin flaA gene. CONCLUSION: Severe bacteremic non-O1, non-O139 V. Cholerae is reported from Laos. The organisms were unusual in being non-motile. They possessed the Vibrio flagellin flaA gene. Further research to determine the reasons for the non-motility and virulence is required.

Biotechnol Bioeng. 2008 Mar 19;
Duan F, March JC

Vibrio Cholerae El Tor serotypes are largely responsible for outbreaks of Cholera in the developing world. The Infection cycle for some strains of V. Cholerae is coordinated, at least in part, through quorum sensing. That is, the expression of virulence genes depends on the concentration of V. Cholerae autoinducers Cholera autoinducer 1 (CAI-1) and autoinducer 2 (AI-2). High concentrations of CAI-1 and AI-2 have been shown previously to inhibit virulence gene expression. We have demonstrated here that a commensal bacterium, E. coli Nissle 1917 (Nissle), can be engineered to express CAI-1 (Nissle expresses AI-2 natively) and effectively interrupt V. Cholerae virulence. We engineered Nissle to express CAI-1 under control of the lac promoter, and demonstrated inhibition of V. Cholerae expression of Cholera toxin (CT, as indicated by presence of the CT subunit B (CTB)) and of the toxin co-regulated pilus (TCP, as indicated by the relative transcript of TCP subunit A (TCPA)) in both monocultures of V. Cholerae and co-cultures with epithelial cells, Nissle, and V. Cholerae. In the model system of Caco-2 epithelia incubated with V. Cholerae, we demonstrated that co-cultures with Nissle expressing CAI-1 activity reduced CTB binding to Caco-2 cells by 63% over co-cultures with wild-type Nissle. Further, cultures with Nissle expressing CAI-1 had significantly lower TCPA transcription than controls with wild-type Nissle. These results represent a significant step towards a prophylactic method for combating enteric disease through engineered quorum signaling within a commensal bacterial strain. Biotechnol. Bioeng. (c) 2008 Wiley Periodicals, Inc.

Infect Immun. 2008 Jul; 76(7): 2958-65
Koizumi Y, Kurita-Ochiai T, Oguchi S, Yamamoto M

Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. We assessed the potential of a nasal vaccine against P. gingivalis Infection for the prevention of atherosclerosis. Apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice were nasally immunized with the 40-kDa outer membrane protein (OMP) of P. gingivalis plus Cholera toxin (CT) as adjuvant and then challenged intravenously with P. gingivalis strain 381. The animals were euthanized 11 or 14 weeks later. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum concentrations of 40-kDa OMP-specific antibodies and cytokines were determined. The areas of the aortic sinus that were covered with atherosclerotic plaque and the serum levels of inflammatory cytokines and chemokines were increased in Apoe(shl) mice challenged with P. gingivalis compared to nonchallenged mice. In comparison, nasal immunization with 40-kDa OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of cytokines and chemokines compared to nonimmunized animals. Nasal immunization also induced 40-kDa OMP-specific serum immunoglobulin G (IgG) and saliva IgA antibody responses. These findings suggest that systemic Infection with P. gingivalis accelerates atherosclerosis in Apoe(shl) mice, and 40-kDa OMP plus CT may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by P. gingivalis in the hyperlipidemic mouse model.

J Virol. 2008 Jul; 82(13): 6288-98
Laniosz V, Holthusen KA, Meneses PI

Viruses may infect cells through clathrin-dependent, caveolin-dependent, or clathrin- and caveolin-independent endocytosis. Bovine papillomavirus type 1 (BPV1) entry into cells has been shown to occur by clathrin-dependent endocytosis, a pathway that involves the formation of clathrin-coated pits and fusion to early endosomes. Recently, it has been demonstrated that the closely related JC virus can enter cells in clathrin-coated vesicles and subsequently traffic to caveolae, the organelle where vesicles of the caveolin-dependent pathway deliver their cargo. In this study, we use immunofluorescence staining of BPV1 pseudovirions to show that BPV1 overlaps with the endosome marker EEA1 early during Infection and later colocalizes with caveolin-1. We provide evidence through the colocalization of BPV1 with transferrin and Cholera toxin B that BPVl trafficking may not be restricted to the clathrin-dependent pathway. Disrupting the entry of caveolar vesicles did not affect BPV1 Infection; however, we show that blocking the caveolar pathway postentry results in a loss of BPV1 Infection. These data indicate that BPV1 may enter by clathrin-mediated endocytosis and then utilize the caveolar pathway for Infection, a pattern of trafficking that may explain the slow kinetics of BPV1 Infection.