Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2012 Nov 10;433(1):220-5.
doi: 10.1016/j.virol.2012.08.014. Epub 2012 Aug 24.

Vironome of Kaposi sarcoma associated herpesvirus-inflammatory cytokine syndrome in an AIDS patient reveals co-infection of human herpesvirus 8 and human herpesvirus 6A

Kristen M Tamburro  1 , Dongmei Yang, Jessica Poisson, Yuri Fedoriw, Debasmita Roy, Amy Lucas, Sang-Hoon Sin, Nadia Malouf, Vincent Moylan, Blossom Damania, Stephan Moll, Charles van der Horst, Dirk P Dittmer
Affiliations
Case Reports

Vironome of Kaposi sarcoma associated herpesvirus-inflammatory cytokine syndrome in an AIDS patient reveals co-infection of human herpesvirus 8 and human herpesvirus 6A

Kristen M Tamburro et al. Virology. .

Abstract

KSHV inflammatory cytokine syndrome (KICS) is a newly described condition characterized by systemic illness as a result of systemic, lytic KSHV infection. We used Illumina sequencing to establish the DNA vironome of blood from such a patient. It identified concurrent high-level viremia of human herpesvirus (HHV) 8 and 6a. The HHV8 plasma viral load was 5,300,000 copies/ml, which is the highest reported to date; this despite less than five skin lesions and no HHV8 associated lymphoma. This is the first report of systemic HHV6a/KSHV co-infection in a patient. It is the first whole genome KSHV sequence to be determined directly from patient plasma rather than cultured or biopsied tumor material. This case supports KICS as a new clinical entity associated with KSHV.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Patient was positive for Kaposi Sarcoma, as confirmed by autopsy, immunohistochemistry, and PCR
(A) LANA (red) and hematoxilin (blue) stain of a lymph node biopsy at 100x, (B) and at 400x. (C–D, arrows) KS lesions in lung at autopsy, (E) Gel of PCR products confirming KSHV positivity. Isolated PBMC DNA was amplified with primers located within the KSHV genes: (1) LANA, (2) vFLIP, (3) K14, (4) vGPCR, (5) Kaposin, (6) Orf69 and GAPDH (“+”) as a reference gene. No primer controls for each sample are indicated by “.” For comparison, KSHV positive PEL DNA was used (“pos”), and a non-template control (NTC) was included as a negative control (“neg”). Molecular weight markers are shown at the beginning and end.
Figure 2
Figure 2. Nextgen sequencing analysis reveals KSHV and HHV6a coinfection
(A) Heatmap and dendrogram of unsupervised single linkage clustering using a Manhattan distance matrix. Reads from individual Illumina lanes were aligned to 3608 whole viral genomes in genbank. For each alignment we computed a score based on the number of hits, coverage and length of the target sequence. (B) Distribution of reads that aligned to the KSHV (NC_003409) genome. Open reading frames are depicted as arrows. (C) Distribution of reads that aligned to the HHV6a (NC_001664) genome. (D) Phylogenetic tree demonstrating alignment of generated consensus sequence for KSHV isolated from patient PBMC, in comparison to previously reported KSHV sequences. BCBL1 sequence was determined from BCBL1 DNA inserted into BAC36 and cloned. GK18 sequence is from cosmid-cloned DNA originating from a classic KS patient. JSC1 sequence is derived from cellular DNA cloned into BAC219. KS biopsy sequence is derived from DNA from KS biopsies, partially digested with Sau3A, cloned into lambda phage, and sequenced. BC1 DNA was sequenced from the PEL-derived cell line, and was cloned into lambda phage and cosmids and sequenced. Our patient sequence is indicated as Consensus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Asou H, Tasaka T, Said JW, Daibata M, Kamada N, Koeffler HP. Co-infection of HHV-6 and HHV-8 is rare in primary effusion lymphoma. Leuk Res. 2000;24:59–61. - PubMed
    1. Boutolleau D, Duros C, Bonnafous P, Caiola D, Karras A, Castro ND, Ouachee M, Narcy P, Gueudin M, Agut H, Gautheret-Dejean A. Identification of human herpesvirus 6 variants A and B by primer-specific real-time PCR may help to revisit their respective role in pathology. J Clin Virol. 2006;35:257–263. - PubMed
    1. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens--Part B: biological agents. Lancet Oncol. 2009;10:321–322. - PubMed
    1. Brandt SJ, Bodine DM, Dunbar CE, Nienhuis AW. Dysregulated interleukin 6 expression produces a syndrome resembling Castleman’s disease in mice. J Clin Invest. 1990;86:592–599. - PMC - PubMed
    1. Chadburn A, Hyjek EM, Tam W, Liu Y, Rengifo T, Cesarman E, Knowles DM. Immunophenotypic analysis of Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman diseases (MCD) Histopathology. 2008;53:513–24. - PubMed

Publication types

MeSH terms