The potential impacts of early secreted antigenic target of 6 kDa of Mycobacterium tuberculosis on KSHV-infected cells.

Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human cancers, including Kaposi's sarcoma (KS) and primary effusion lymphoma, which are mostly seen in immunocompromised patients, such as human immunodefeciency virus (HIV)+ individuals. Tuberculosis (TB), caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb), remains one of the deadliest infectious diseases in the world. The risk of developing TB is dramatically higher in people living with HIV than among those without HIV infection. Case reports link cutaneous or pulmonary KS in HIV+ patients with mycobacterial co-infections, however, impacts of Mtb infection or its products on KSHV-infected cells are not known. We report here that ESAT-6, a secreted Mtb virulence factor, induces viral reactivation from KSHV-infected cells. KSHV-infected pulmonary endothelial cells were resistant to ESAT-6 induced inhibition of cell growth. Our data demonstrate that Mtb virulence factors influence the biology of KSHV-infected cells, highlighting the need to study the interactions between these two pathogens commonly found in people living with HIV.

Author Correction: R-loop-forming Sequences Analysis in Thousands of Viral Genomes Identify A New Common Element in Herpesviruses.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

R-loop-forming Sequences Analysis in Thousands of Viral Genomes Identify A New Common Element in Herpesviruses.

R-loops are RNA-DNA hybrid sequences that are emerging players in various biological processes, occurring in both prokaryotic and eukaryotic cells. In viruses, R-loop investigation is limited and functional importance is poorly understood. Here, we performed a computational approach to investigate prevalence, distribution, and location of R-loop forming sequences (RLFS) across more than 6000 viral genomes. A total of 14637 RLFS loci were identified in 1586 viral genomes. Over 70% of RLFS-positive genomes are dsDNA viruses. In the order Herpesvirales, RLFS were presented in all members whereas no RLFS was predicted in the order Ligamenvirales. Analysis of RLFS density in all RLFS-positive genomes revealed unusually high RLFS densities in herpesvirus genomes, with RLFS densities particularly enriched within repeat regions such as the terminal repeats (TRs). RLFS in TRs are positionally conserved between herpesviruses. Validating the computationally-identified RLFS, R-loop formation was experimentally confirmed in the TR and viral Bcl-2 promoter of Kaposi sarcoma-associated herpesvirus (KSHV). These predictions and validations support future analysis of RLFS in regulating the replication, transcription, and genome maintenance of herpesviruses.