Infection with Kaposi’s Sarcoma herpesvirus (KSHV) has been linked to multiple cancers including Kaposi’s sarcoma (KS), Primary effusion lymphoma (PEL), and Multicentric Castleman’s disease (MCD). One of the hallmarks of transformed cancer cells is the activity of telomere maintenance mechanisms. The present study uncovers the onset of Alternative lengthening of telomeres (ALT) in response to KSHV infection from a proteomic screen of telomere-associated DNA damage response proteins by Proteomics of isolated chromatin fragments (PICh). In several initially telomerase+ cell lines, features of ALT activation are present in response to KSHV infection including increased telomere sister-chromatid exchanges, C-circles, telomere clustering in interphase, ALT-associated proteins at telomere clusters, and telomere fragility. Binding of shelterin to telomeric DNA was increased upon infection with KSHV. Interestingly, cells which are latently infected with KSHV are dependent on ALT factors for their efficient proliferation in clonogenic assays and such factors may be essential for the maintenance of viral episomes in infected cells as shown by episome qPCR. Moreover, preliminary experiments by ChIP indicate an increase in heterochromatin marks at telomeres upon infection, similar to the marks documented on the KSHV episome. Analysis of primary tumour material from 8 KS and 7 PEL patients suggests that this not limited to the in vitro systems considered in this study. Taken together, this work demonstrates for the first time the capability of latent KSHV to trigger telomere maintenance via ALT and suggests a model in which KSHV episomes are replicated in tandem with telomeres by BIR in such cells. This provides a unique susceptibility of KSHV infected cancer cells to inhibition of ALT, which may be utilized for the trial of future treatment for KSHV-associated cancers.