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Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections

Overview of attention for article published in Journal of Virology, September 2018
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Title
Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections
Published in
Journal of Virology, September 2018
DOI 10.1128/jvi.01138-18
Pubmed ID
Authors

Sang-Hoon Sin, Anthony B. Eason, Rachele Bigi, Yongbaek Kim, SunAh Kang, Kelly Tan, Tischan A. Seltzer, Raman Venkataramanan, Hyowon An, Dirk P. Dittmer

Abstract

Kaposi Sarcoma-associated herpesvirus (KSHV) KSHV induces B cell hyperplasia and neoplasia such as multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). To explore KSHV-induced B cell reprogramming in vivo, we expressed the KSHV latency locus, inclusive of all viral miRNAs, in B cells of transgenic mice in the absence of the inhibitory FcγRIIB receptor. The BALB/c strain was chosen as this is the preferred model to study B cell differentiation. The mice developed hyperglobulinemia, plasmacytosis, and B lymphoid hyperplasia. This phenotype was ameliorated by everolimus, which is a rapamycin-derivative approved for the treatment of mantle cell lymphoma. KSHV-latency mice exhibited hyperresponsiveness to the T-dependent (TD) antigen mimic α-CD40 and increased incidence of pristane-induced inflammation. Lastly, the adaptive immunity against a secondary infection with Zika virus (ZIKV) was markedly enhanced. These phenotypes are consistent with KSHV lowering the activation threshold of latently-infected B cells, which may be beneficial in endemic areas, where KSHV is acquired in childhood and where infections are common.IMPORTANCE Kaposi sarcoma-associated herpesvirus (KSHV) establishes latency in B cells and is stringently linked to primary effusion lymphoma (PEL) and the pre-malignant B cell hyperplasia multicentric Castleman's disease (MCD). To investigate potential genetic background effects, we expressed the KSHV miRNAs in BALB/c transgenic mice. BALB/c are the preferred strain for B cell hybridoma development because of their propensity to develop predictable B cell responses to antigen. The BALB/c-latency mice exhibited a higher incidence of B cell hyperplasia as well as sustained hyperglobulinemia. The development of neutralizing antibodies against ZIKV was augmented in BALB/c-latency mice. Hyperglobulinemia was dampened by everolimus, a derivative of rapamycin, suggesting a role for mTOR inhibitors in managing immune activation, which is hallmark of KSHV infection as well as HIV infection.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 21%
Researcher 7 21%
Student > Doctoral Student 3 9%
Student > Bachelor 2 6%
Student > Ph. D. Student 1 3%
Other 3 9%
Unknown 10 30%
Readers by discipline Count As %
Immunology and Microbiology 6 18%
Medicine and Dentistry 6 18%
Agricultural and Biological Sciences 3 9%
Mathematics 1 3%
Business, Management and Accounting 1 3%
Other 4 12%
Unknown 12 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 September 2018.
All research outputs
#17,292,294
of 25,385,509 outputs
Outputs from Journal of Virology
#22,057
of 25,700 outputs
Outputs of similar age
#224,510
of 347,925 outputs
Outputs of similar age from Journal of Virology
#135
of 184 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 25,700 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.5. This one is in the 9th percentile – i.e., 9% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 347,925 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 184 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.