Absence of Kaposi's sarcoma-associated herpesvirus in patients with pulmonary arterial hypertension

RATIONALE: In addition to Kaposi's sarcoma, Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) has been associated with two other diseases: primary effusion lymphoma and the plasma cell variant of multicentric Castleman's disease. Recently, evidence of KSHV infection was reported in plexiform lesions of idiopathic pulmonary arterial hypertension (IPAH) as well as in adjacent parenchyma and bronchial epithelial cells. OBJECTIVES: To further investigate a possible association of KSHV and pulmonary arterial hypertension. METHODS AND MEASUREMENTS: Twenty-six lungs explanted from German patients suffering from IPAH were tested for the presence of KSHV antigen and genomes by immunohistochemistry (IHC) and polymerase chain reaction (PCR). MAIN RESULTS: When stained with a commercial monoclonal antibody directed against the latency-associated nuclear antigen of KSHV, LANA-1, a positive signal reminiscent of the "speckled" nuclear pattern typical of latently KSHV-infected cells was found in 16 (61.5%) cases. Alveolar and bronchial epithelial cells in areas of unremarkable lung tissue, but not cells within the plexiform lesions, were the predominantly stained cell types. Different KSHV-PCR assays (based on orf26, orfK6, and orf72) performed on samples that had tested positively in IHC, however, could not confirm KSHV infection, indicating that the IHC signal was not due to KSHV infection. One IHC-negative patient tested positive by PCR. A PCR based on consensus degenerate hybrid oligonucleotide primers (CODEHOP) to detect yet unknown gamma-herpesviruses did not reveal any specific sequences. CONCLUSIONS: KSHV is unlikely to play a role in the pathogenesis of IPAH.     

Lack of MERS Coronavirus Neutralizing Antibodies in Humans,Eastern Province,Saudi Arabia

We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.     

Influence of HLA alleles on shedding of Kaposi sarcoma-associated herpesvirus in saliva in an African population

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in sub-Saharan Africa. Infection in childhood involves mother-to-child transmission and transmission between siblings or other close contacts. Large amounts of viral DNA in saliva have been linked to transmission from mother to child. To investigate factors contributing to the shedding of KSHV in the saliva of mothers in rural South Africa, we sequenced the HLA-A alleles of 448 mothers and the HLA-DRB1 alleles of 363 mothers and compared their HLA types with viral loads in saliva. METHODS: Viral load was quantified with real-time polymerase chain reaction on DNA extracted from saliva. HLA-A and HLA-DRB1 allele groups were determined by sequencing-based typing. RESULTS: We found that 2 HLA-A alleles, A*6801 and A*4301, and 1 HLA-DRB1 allele group, DRB1*04, were associated with shedding of KSHV in saliva. KSHV could be detected more frequently in mothers carrying at least 1 copy of HLA-A*6801 or HLA-A*4301, and higher viral loads were found in HLA-A*68- and HLA-DRB1*04-carrying mothers. CONCLUSIONS: These findings could suggest that 2 HLA-A alleles, A*6801 and A*4301, and 1 HLA-DRB1 allele group, DRB1*04, that are more frequent in African populations might be associated with an impaired control of KSHV and, hence, increased shedding in saliva.     

Mother-to-child transmission of human herpesvirus-8 in South Africa

To investigate transmission of human herpesvirus (HHV)-8, 2546 mother-child pairs were recruited from rural clinics in South Africa and were tested for antibodies against lytic and latent HHV-8 antigens. The prevalence of antibodies in children increased with increasing maternal antibody titer (lytic, chi 21=26, and P<.001; latent, chi 21=55, and P<.001). HHV-8 DNA was detectable in 145 of 978 maternal saliva samples (mean virus load, 488,450 copies/mL; range, 1550-660,000 copies/mL) and in 12 of 43 breast-milk samples (mean virus load, 5800 copies/mL; range, 1550-12,540 copies/mL). The prevalence of HHV-8 DNA in maternal saliva was unrelated to latent anti-HHV-8 antibody status but was higher in mothers with the highest titers of lytic antibodies than in other mothers (34% vs. 8%; P<.001). The prevalence of lytic anti-HHV-8 antibodies in children was 13% (70/528) if the mother did not have HHV-8 in saliva and was 29% (8/28) if the mother had a high HHV-8 load (>50,000 copies/mL) in saliva (odds ratio, 2.6; 95% confidence interval, 1.1-6.2). The presence of HHV-8 DNA in maternal saliva was unrelated to latent antibodies in children. Saliva could be a route of transmission of HHV-8 from person to person, although other routes cannot be ruled out.     

Genotypic analysis of two hypervariable human cytomegalovirus genes

Most human cytomegalovirus (HCMV) genes are highly conserved in sequence among strains, but some exhibit a substantial degree of variation. Two of these genes are UL146, which encodes a CXC chemokine, and UL139, which is predicted to encode a membrane glycoprotein. The sequences of these genes were determined from a collection of 184 HCMV samples obtained from Africa, Australia, Asia, Europe, and North America. UL146 is hypervariable throughout, whereas variation in UL139 is concentrated in a sequence encoding a potentially highly glycosylated region. The UL146 sequences fell into 14 genotypes, as did all previously reported sequences. The UL139 sequences grouped into 8 genotypes, and all previously reported sequences fell into a subset of these. There were minor differences among continents in genotypic frequencies for UL146 and UL139, but no clear geographical separation, and identical nucleotide sequences were represented among communities distant from each other. The frequent detection of multiple genotypes indicated that mixed infections are common. For both genes, the degree of divergence was sufficient to preclude reliable sequence alignments between genotypes in the most variable regions, and the mode of evolution involved in generating the genotypes could not be discerned. Within genotypes, constraint appears to have been the predominant mode, and positive selection was detected marginally at best. No evidence was found for linkage disequilibrium. The emerging scenario is that the HCMV genotypes developed in early human populations (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times.