Latent Herpes Simplex Virus Type Research Articles

Latent herpes simplex virus type 1 DNA contains two copies of the virion DNA joint region.

Southern blot analysis of latent herpes simplex virus DNA detected in mouse brain and digested with a restriction enzyme revealed two copies of the virion DNA joint fragment. Thus, the absence of free ends noted previously in latent herpes simplex virus type 1 DNA is due to joining of the termini.

Retrieval of latent herpes simplex virus type 1 genetic information from murine trigeminal ganglia by superinfection with heterotypic virus in vivo.

Mice previously latently infected with the F strain of herpes simplex virus type 1 (HSV-1) can be successfully colonized with a second virus strain if HSV-2 is introduced at the same peripheral site as HSV-1. On the other hand, HSV-1 strains seemed able mutually to exclude establishment of latency with each other. Mice (3 months or 3 years after nasal infection) latently infected with HSV-1 were thus superinfected with HSV-2. The mice were sacrificed 2 days post-infection when HSV-2 replication in the ganglia was found to have commenced. Ganglia were homogenized immediately and virus was plaqued on permissive cells. HSV-1 plaques were regularly obtained among HSV-2 plaques as assessed by staining with an enzyme-linked immunosorbent using a type-specific monoclonal antibody recognizing glycoprotein C of HSV-1. DNA from this virus had identical restriction endonuclease patterns (EcoRI, BamHI and HindIII) to the F strain used to infect the animals latently. HSV-1 was not retrieved from ganglia of controls superinfected with a neuroadapted vaccinia virus or were mock-superinfected. The results suggest that it is possible to superinfect a latently infected ganglionic neuronal cell with a heterotypic HSV strain and that the subsequently introduced HSV-2 can act in trans to induce reactivation of latent HSV-1.

Detection of multiple strains of latent herpes simplex virus type 1 within individual human hosts.

One hundred and fifteen isolates of herpes simplex virus were recovered from parallel explant cultures of trigeminal and vagus ganglia and trigeminal nerve roots derived from 20 unselected human cadavers. Restriction enzyme patterns of strains recovered from 18 of 20 individuals could be differentiated from individual to individual, although all isolates from a single host were identical. Isolates from two individuals differed among themselves in the number and location of certain restriction enzyme sites.

Inhibition by indomethacin of in vitro reactivation of latent herpes simplex virus type 1 in murine trigeminal ganglia.

Infectious virus could no longer be detected in the trigeminal ganglia removed from mice 25 days after infection with herpes simplex virus type 1 (HSV-1) by the lip route. When the ganglia were cultured in vitro for 1 or 2 days, infectious HSV-1 was again detected in the ganglia, indicating the reactivation of latent HSV-1. The effect of indomethacin on this reactivation was examined. When the ganglia were cultivated in the presence of 5 X 10(-4) M-indomethacin, the appearance of infectious virus in the ganglia was almost completely inhibited. After removal of indomethacin, infectious virus appeared and the virus titre reached levels found in the ganglia cultured in indomethacin-free medium, indicating that the inhibition of the reactivation may not be due to the cytotoxic effect of indomethacin on the ganglionic cells. The inhibitory effect of indomethacin was only seen when it was added shortly after explantation. These results suggest that indomethacin affects some early processes of viral reactivation in the explanted ganglia. The synthesis of prostaglandins (PGE and PGB) found in the explanted ganglia was strongly suppressed by indomethacin, as was the viral reactivation. Other inhibitors of prostaglandin synthesis, i.e. tetracaine, mepacrine and mefenamic acid, also inhibited viral reactivation in the explanted ganglia. These results suggest that the inhibitory effect of indomethacin on the reactivation of latent HSV-1 may be due to the inhibition of prostaglandin synthesis, although it is possible that other cellular changes which could be caused by indomethacin contributed to the suppression of reactivation.

Effect of intensive acyclovir therapy during artificial reactivation of latent herpes simplex virus.

The chemotherapeutic effect of intensive acyclovir (ACV) treatment was evaluated in New Zealand white rabbits with confirmed latent herpes simplex virus type 1 (HSV-1). Acyclovir was administered orally (1 mg/ml of drinking water), topically (three times per day), and intramuscularly (16.5 mg/kg body wt twice per day) beginning 36 days after ocular inoculation and continued for 4 consecutive weeks, during which time the rabbits underwent concurrent stimulation by bilateral iontophoresis of 0.01% epinephrine into the cornea to induce reactivation of latent virus. None of the eight rabbits receiving intensive ACV shed virus in their tear film sample during 4 weeks of concurrent epinephrine iontophoresis and antiviral therapy. All five rabbits receiving placebo treatment shed HSV in tear film samples. The total number of positive ocular samples was 14 during the first week of dual treatment (5/5 animals positive) and decreased to 2 positive samples (2/5 animals) during the fourth week of dual treatment. Upon sacrifice, HSV was isolated from 8 of 16 trigeminal ganglia of ACV-treated animals and 6 of 10 placebo-treated animals. No increased resistance to ACV was detectable in any of the virus isolated from trigeminal ganglia. Antibody and cellular immune responses were not significantly different between the ACV-treated and placebo-treated groups.

Effects of adenosine monophosphate on the reactivation of latent herpes simplex virus type 1 infections of mice.

Adenosine monophosphate pretreatment of mice with latent herpes simplex virus type 1 infections significantly reduced the rate of reactivation of latent virus. Adenosine monophosphate pretreatment did not, however, eradicate latent virus.

A primate model for age and host response to genital herpetic infection: determinants of latency.

Thirty five female Cebus albifrons monkeys (16 adolescents and 19 adults) were infected vaginally with herpes simplex virus (HSV) type 2. Fifteen developed spontaneous recurrent genital HSV infections. All 35 were killed for study eight to 12 months after primary infection, and tissue from the vagina, cervix, uterus, ovary, paracervical autonomic plexus, and lumbosacral dorsal root ganglia of eight animals. Host age was the most important variable influencing viral latency; 69% of adolescents and 42% of adults had latent HSV type 2 infections. Animals that developed latent infections were significantly easier to infect, shed virus during the primary infection significantly longer, and had more severe primary disease than those who did not become latently infected.

Latent infections of sensory ganglia as influenced by phosphonoformate treatment of herpes simplex virus-induced skin infections in hairless mice.

Topical treatment with 3% phosphonoformate of herpes simplex virus type 1 (HSV)-induced skin infections of hairless mice reduced the severity of skin lesions when the treatment was initiated 3 h after virus inoculation in the lumbosacral area or 3 and 24 h after inoculation in the orofacial area. The mortality was significantly reduced in lumbosacral-infected mice and was completely prevented in orofacial-infected mice when the treatment was initiated with a delay of 24 h after virus inoculation. However, phosphonoformate did not prevent the establishment of latent herpes simplex virus type 1 infections in the spinal and trigeminal ganglia, even when treatment was initiated as early as 3 h after infection.