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

J Med Virol. 2021 Jun;93(6):4028-4032. doi: 10.1002/jmv.26291. Epub 2020 Jul 17.

Abstract

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.

Keywords: ESAT-6; HIV; KSHV; Kaposi's sarcoma; mycobacterium tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / genetics*
  • Antigens, Bacterial / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / pharmacology
  • Cell Line, Tumor
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / microbiology
  • Endothelial Cells / virology
  • Gene Expression Regulation, Viral
  • Herpesvirus 8, Human / physiology*
  • Humans
  • Lung / cytology
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / pathogenicity
  • Sarcoma, Kaposi / virology*
  • Virulence Factors
  • Virus Activation*
  • Virus Replication

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Virulence Factors