scholarly journals Vesicular Stomatitis Virus Genomic RNA Persists In Vivo in the Absence of Viral Replication

2009 ◽  
Vol 84 (7) ◽  
pp. 3280-3286 ◽  
Author(s):  
Ian D. Simon ◽  
Nico van Rooijen ◽  
John K. Rose

ABSTRACT Our previous studies using intranasal inoculation of mice with vesicular stomatitis virus (VSV) vaccine vectors showed persistence of vector genomic RNA (gRNA) for at least 60 days in lymph nodes in the absence of detectable infectious virus. Here we show high-level concentration of virus and gRNA in lymph nodes after intramuscular inoculation of mice with attenuated or single-cycle VSV vectors as well as long-term persistence of gRNA in the lymph nodes. To determine if the persistence of gRNA was due to ongoing viral replication, we developed a tagged-primer approach that was critical for detection of VSV mRNA specifically. Our results show that VSV gRNA persists long-term in the lymph nodes while VSV mRNA is present only transiently. Because VSV transcription is required for replication, our results indicate that persistence of gRNA does not result from continuing viral replication. We also performed macrophage depletion studies that are consistent with initial trapping of VSV gRNA largely in lymph node macrophages and subsequent persistence elsewhere in the lymph node.

2006 ◽  
Vol 81 (4) ◽  
pp. 2078-2082 ◽  
Author(s):  
Ian D. Simon ◽  
Jean Publicover ◽  
John K. Rose

ABSTRACT Live-attenuated vesicular stomatitis virus (VSV) vectors expressing foreign antigens induce potent immune responses and protect against viral diseases in animal models. Highly attenuated (VSV-CT1) or single-cycle VSV (VSVΔG) vectors induce immune responses lower than those generated by attenuated wild-type VSV vectors when given intranasally. We show here that reduced spread of the more highly attenuated or single-cycle vectors to other organs, including lymph nodes, correlates with the reduction in the immune responses. A reverse transcription, real-time PCR assay for VSV genomic RNA (gRNA) sequences showed long-term persistence of gRNA from replicating vectors in lymph nodes, long after viral clearance. Such persistence may be important for induction of potent immune responses by VSV vectors.


Vaccine ◽  
2007 ◽  
Vol 25 (4) ◽  
pp. 741-750 ◽  
Author(s):  
Amy Palin ◽  
Anasuya Chattopadhyay ◽  
Steven Park ◽  
Guillaume Delmas ◽  
Rema Suresh ◽  
...  

2006 ◽  
Vol 50 (6) ◽  
pp. 2231-2233 ◽  
Author(s):  
Xing-Quan Zhang ◽  
Meredith Sorensen ◽  
Michael Fung ◽  
Robert T. Schooley

ABSTRACT Recently, antiretroviral agents directed at several steps involved in viral entry have been shown to reduce viral replication in vitro and in vivo. We have demonstrated a high level of in vitro synergistic antiretroviral activity for two entry inhibitors that are directed at sequential steps in the entry process.


2021 ◽  
Author(s):  
Takefumi Yoshida ◽  
Fumihiko Fujita ◽  
Dai Shida ◽  
Kenichi Koushi ◽  
Kenji Fujiyoshi ◽  
...  

Abstract Background. The extent of lymph node dissection in advanced colorectal cancer varies according to regional guidelines. D3 lymphadenectomy is routinely performed in Japan but is associated with several risk factors. Metastases of the main lymph nodes (No.253 lymph nodes), which are located at the root of the inferior mesenteric artery, are rare in left-sided colorectal cancer. Tumor depth (T4) is an identifier of No.253 lymph node metastasis (LNM) risk, but other risk factors associated with No.253 LNM are unclear. This study was undertaken to investigate the frequency of No.253 LNM and to identify other clinicopathological risk factors associated with No.253 LNM in left-sided colorectal cancer. In this study, we aimed to evaluate the clinical benefit of routine D3 lymphadenectomy in surgically treated advanced colorectal cancer. Methods. A retrospective database of patients with colorectal cancer who underwent D3 dissection and R0 resection at Kurume University Hospital from 1978 to 2017 was constructed and used to search for the frequency and risk factors of No.253 LNM to investigate long-term prognosis. Clinicopathological factors associated with No.253 LNM, including age, sex, tumor location, T stage, tumor diameter, carcinoembryonic antigen levels, and various dissected lymph nodes, were analyzed. Results. Among 1,614 consecutive patients, No.253 LNM was observed in 23 cases (1.4%). The presence of three or more regional LNMs was an independent risk factor for No.253 LNM (odds ratio: 26.8). The 5-year overall survival rate was 49.1% in the No.253 LNM-positive group and 78.4% in the No.253 LNM-negative group (p=0.002). Conclusion. In left-sided colorectal cancer, No.253 LNM was a poor prognosis factor, and three or more regional LNMs were a risk factor for No.253 LNM. The No.253 LNM-positive group had a poor prognosis, but there are cases of long-term survival, with a 5-year survival rate of 49%. D3 lymphadenectomy is suitable when three or more metastatic LNs are identified prior to surgery.


Vaccine ◽  
2009 ◽  
Vol 27 (22) ◽  
pp. 2930-2939 ◽  
Author(s):  
J. Erik Johnson ◽  
John W. Coleman ◽  
Narender K. Kalyan ◽  
Priscilla Calderon ◽  
Kevin J. Wright ◽  
...  

2001 ◽  
Vol 114 (19) ◽  
pp. 3463-3477
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Valentin Grabovsky ◽  
Jürgen Moll ◽  
Jonathan Sleeman ◽  
Peter Herrlich ◽  
...  

Cell motility is an essential element of tumor dissemination, allowing organ infiltration by cancer cells. Using mouse LB lymphoma cells transfected with standard CD44 (CD44s) cDNA (LB-TRs cells) or with the alternatively spliced CD44 variant CD44v4-v10 (CD44v) cDNA (LB-TRv cells), we explored their CD44-dependent cell migration. LB-TRv cells, but not LB-TRs or parental LB cells, bound soluble hyaluronic acid (HA) and other glycosaminoglycans (GAGs), and exclusively formed, under physiological shear force, rolling attachments on HA substrate. Furthermore, LB-TRv cells, but not LB-TRs cells or their parental LB cells, displayed accelerated local tumor formation and enhanced accumulation in the peripheral lymph nodes after s.c. inoculation. The aggressive metastatic behavior of i.v.-injected LB-TRV cells, when compared with that of other LB-transfectants, is attributed to more efficient migration to the lymph nodes, rather than to local growth in the lymph node. Injection of anti-CD44 monoclonal antibody or of the enzyme hyaluronidase also prevented tumor growth in lymph nodes of BALB/c mice inoculated with LB-TRv cells. The enhanced in vitro rolling and enhanced in vivo local tumor growth and lymph node invasion disappeared in LB cells transfected with CD44v cDNA bearing a point mutation at the HA binding site, located at the distal end of the molecule constant region. These findings show that the interaction of cell surface CD44v with HA promotes cell migration both in vitro and in vivo, and they contribute to our understanding of the mechanism of cell trafficking, including tumor spread.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Lei Huang ◽  
Jianning Deng ◽  
Ren Lang ◽  
Guoyang Liao ◽  
Wei Jiang

An increased level of microbial translocation has been observed in HIV-infected individuals. The host response to microbial translocation is compromised in HIV-infected progressors but remains unknown in HIV-infected long-term nonprogressors (LTNPs). To evaluate microbial translocation in HIV, we assessed lipopolysaccharide (LPS) immunohistochemistry staining in lymph nodes. We found enriched bacterial LPS immunohistochemistry staining in the germinal center of a lymph node from an HIV-infected LTNP, evenly distributed from three progressors with impaired germinal center structures and rarely detected from two HIV-negative individuals. The impaired germinal center structures were consistent with collagen deposition in lymph nodes using immunohistochemistry staining. These results suggest greater immune responses against bacterial LPS translocation in LTNPs, which may reveal an important mechanism in controlling microbial translocation and disease progression in HIV LTNPs.


1968 ◽  
Vol 127 (2) ◽  
pp. 307-325 ◽  
Author(s):  
Vera S. Byers ◽  
Eli E. Sercarz

A set of conditions has been described under which primed rabbit lymph nodes produce a secondary antibody response upon in vivo stimulation with a large dose of antigen, but are subsequently "exhausted;" that is, lymph node cultures prepared at intervals following the booster injection cannot be re-stimulated to display tertiary responses. Rabbits given 100-fold less antigen in the booster inoculum were able to give a tertiary response upon in vitro challenge. The system used permits neither induction nor continuation of a primary response to BSA in vitro. Since it could be demonstrated that no memory cells were generated by the booster injection within the intervals between in vivo injection and culture, the tertiary response in nonexhausted nodes must have been due to residual memory cells which remained untriggered by the in vivo booster injection. The unresponsive state was not caused by antibody feedback. These results are interpreted to mean that a population of memory cells can be exhausted by a supraoptimal dose of antigen, rendering the node temporarily incapable of further response. This implies that long-lived memory is not due to asymmetric division of memory cells. The source and fate of memory cells is discussed with regard to this evidence.


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