Activation of Human Immunodeficiency Virus by Herpes Simplex Virus

Abstract

Heterologous viruses have been examined for their ability to accelerate the course of infection with the human immunodeficiency virus (HIV) type 1. In this study, ACH-2 cells persistently infected with HIV-1 exhibited augmented HIV-1 replication as a result of superinfection with herpes simplex virus (HSV) type 1. Using HSV-1 mutants with deletions in the genes encoding immediate-early proteins ICP0, ICP4, and ICP27, it was found that ICP0 and ICP27, but not ICP4, were essential for up-regulation of HIV replication. Northern blot analysis showed that this activation of HIV was characterized by an initial rise in the level of the small, subgenomic (2.0 and 4.3 kb) mRNA species, followed by an increase in the level of unspliced genomic (9.2 kb) mRNA. Such a shift in transcriptional phase recapitulates the early-to-late transition seen in single-step growth curves of acute HIV-1 infection. Thus, HSV can activate HIV-1 from latency in ACH-2 cells, this activation of HIV is independent of productive HSV replication since the delta ICP4 deletion mutant is replication-incompetent, and this activation is evident as an increase in the steady-state levels of HIV transcripts.

Herpes Simplex Virus Type 2 Enhances HIV-1 Susceptibility by Affecting Langerhans Cell Function

“…Notably, HSV-2 replication is not required for the observed increase in HIV-1 transmission, suggesting that virus particles present at lesions might already affect LC function. Various studies showed that HSV can increase HIV-1 replication at several levels (43)(44)(45), and this might also affect HIV-1 infection of LCs. However, our data showed that HSV-2 replication is not required, because UV-HSV-2 induced HIV-1 infection and transmission to a similar level as replicationcompetent HSV-2.…”

Consistent Inhibition of HIV-1 Replication in CD4 + T Cells by Acyclovir without Detection of Human Herpesviruses

“…There is evidence of more rapid HIV-1 disease progression in dually infected individuals (6,15,29) as well as in vitro data demonstrating that HSV-2 proteins can activate the HIV-1 long terminal repeat, leading to increased HIV-1 replication (10,18,23). Recent trials of acyclovir monotherapy for HSV-2 infection in HSV-2/HIV-1-coinfected individuals showed an approximately 0.33 to 0.5 log 10 decrease in HIV-1 plasma levels, but the overall benefits of this approach remain unclear (24,30,36).…”

Sexually-transmitted viral diseases in women: clinical and epidemiological aspects and advances in laboratory diagnosis

“…Activation of these lymphocytes previously infected by HIV leads to a greater replication of the former virus in response to the HSV infection [90]. During reactivation, as well as stimulating the CD 4 + lymphocytes, some HSV proteins seem to trans-activate the long terminal repeat of HIV, increasing replication [91][92]. In a study by Schacker et al, HIV RNA was detected in 25/26 episodes of HSV reactivation, in independent titers of the HIV plasmatic viral load [90].…”