title: Human herpesvirus 8 reactivation and human immunodeficiency virus type 1 gp120.
abstract: BACKGROUND
  Human herpesvirus 8 (HHV-8) is the presumed etiologic agent of Kaposi sarcoma (KS), the most common neoplasm in patients with acquired immunodeficiency syndrome. Current evidence indicates HHV-8 is necessary, but not sufficient, for KS development without the involvement of other cofactors. One potentially important cofactor is human immunodeficiency virus type 1 (HIV-1). Although HIV-1 is not essential for development of KS, studies have shown factors released from HIV-1-infected cells, including HIV-1 proteins and cytokines, promote the growth of KS cells in vitro. Recently, studies have shown that coculture of HIV-1-infected T cells with HHV-8-infected primary effusion lymphoma cell lines results in HHV-8 reactivation. This response was due, in part, to cytokines. However, only a portion of induced HHV-8 replication could be accounted for by cytokine stimulation, indicating that other factors, including HIV-1-associated proteins, may also be involved.
  
  
  OBJECTIVE
  To investigate a possible role for HIV-1 gp120 in HHV-8 reactivation.
  
  
  METHODS
  Using an in vitro model system, we examined the effect of recombinant HIV-1 gp120 protein on HHV-8 replication in latently infected primary effusion lymphoma cell lines.
  
  
  METHODS
  Reactivation of HHV-8 was analyzed using Northern blot analysis and quantitative polymerase chain reaction for ORF26 messenger RNA expression, a gene encoding for the HHV-8 minor capsid protein produced only during reactivation. The results were extended and confirmed using a luciferase reporter construct driven by the HHV-8 ORF50 promoter, the first promoter activated during HHV-8 replication.
  
  
  RESULTS
  No evidence of enhanced HHV-8 replication was found following treatment with HIV-1 gp120. In addition, HIV-1 gp120 was unable to act synergistically with interferon-gamma or hepatocyte growth factor/scatter factor to enhance reactivation of the virus in infected primary effusion lymphoma cell lines.
  
  
  CONCLUSIONS
  HIV-1 gp120 does not appear to be responsible for the reactivation of HHV-8 demonstrated in our previous studies. Further studies are necessary to determine if other HIV-associated proteins, particularly Tat, gp160, and/or gp41, which are also released from infected cells, may be important in inducing HHV-8 reactivation.
authors.affiliation: Department of Pathology and Skin Cancer Research Laboratories, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, Ill 606153, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Lu
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Gordon
authors.forename: Bala
authors.initials: B
authors.lastname: Chandran
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Foreman
mesh_terms: D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D015699:HIV Envelope Protein gp120