scholarly journals The Influence of Cyclosporin Immunosuppression on the Efficacy of Famciclovir or Valaciclovir Chemotherapy Studied in a Murine Herpes Simplex Virus Type 1 Infection Model

1997 ◽  
Vol 8 (4) ◽  
pp. 317-326 ◽  
Author(s):  
AM Thackray ◽  
HJ Field

Mice with or without immunosuppression by cyclosporin (Cy) were inoculated with herpes simplex virus type 1 in the ear pinna. Without immunosuppression, 20% of the mice died; clinical signs resolved in survivors and infectious virus was cleared by 7 to 10 days post-inoculation (p.i.). With Cy, mortality was 50%, clinical signs increased and infectious virus persisted. Mice were treated with either valaciclovir (VACV) or famciclovir (FCV) from days 1–5 or 5–10 p.i. and both compounds moderated the disease, but only FCV led to rapid restoration of body weight and complete protection from mortality. Resolution of clinical signs was more marked with immunosuppression. On cessation of VACV therapy, infectious virus recurred on individual days. Without immunosuppression, recurrence was detected in neural tissues only, but with Cy, infectious virus also recurred in skin. No recurrences of infectious virus were observed in any FCV-treated mice.

1997 ◽  
Vol 60 (10) ◽  
pp. 1259-1261 ◽  
Author(s):  
D. BARDELL

Droplets of saliva containing herpes simplex virus type 1 were placed on the skin of tomatoes and the upper surface of lettuce leaves. There was no loss of virus infectivity titer at refrigerator temperature (2°C) at any time examined up to 1 h, the longest period tested. At room temperature (22 to 24°C) there was a 2-log drop in titer between 30 and 60 min, but some infectious virus was still present at 1 h. The virus-containing saliva remained in a liquid state at 2°C. At 22 to 24°C the droplets became dry at approximately 50 min. Implications of the findings are discussed.


2007 ◽  
Vol 81 (14) ◽  
pp. 7380-7387 ◽  
Author(s):  
Colin M. Crump ◽  
Catherine Yates ◽  
Tony Minson

ABSTRACT The assembly and egress of herpesviruses are complex processes that require the budding of viral nucleocapsids into the lumen of cytoplasmic compartments to form mature infectious virus. This envelopment stage shares many characteristics with the formation of luminal vesicles in multivesicular endosomes. Through expression of dominant-negative Vps4, an enzyme that is essential for the formation of luminal vesicles in multivesicular endosomes, we now show that Vps4 function is required for the cytoplasmic envelopment of herpes simplex virus type 1. This is the first example of a large enveloped DNA virus engaging the multivesicular endosome sorting machinery to enable infectious virus production.


2000 ◽  
Vol 44 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Alana M. Thackray ◽  
Hugh J. Field

ABSTRACT Young adult mice were inoculated with herpes simplex virus type 2 (HSV-2) in the ear pinna. A relatively severe infection resulted, and 45% of the mice died by 11 days postinfection. Therapy at 1 mg/ml by means of the drinking water with either famciclovir for periods of 5 or 10 days or valaciclovir for 5, 10, 15, or 20 days decreased clinical signs and reduced mortality to 15% or less. Throughout a period of 27 days, mice were tested daily for the presence of infectious virus in the ear pinna, brain stem, and ipsilateral trigeminal ganglia. Virus was cleared from these tissues in surviving, untreated animals by 12 days postinfection, and no infectious virus was detected subsequently in any tissue. Furthermore, no infectious virus was detected after day 9 in mice that had been treated with famciclovir. In mice that had received valaciclovir therapy, however, infectious virus was repeatedly detected in the trigeminal ganglia and brain stem tissue samples up to 7 days after treatment was discontinued. To date, no specific mechanism to account for these results has been discovered; however, possible mechanisms for the persistence of potentially infectious virus in neural tissue of treated mice are discussed.


Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1201-1210 ◽  
Author(s):  
M. Labetoulle ◽  
P. Kucera ◽  
G. Ugolini ◽  
F. Lafay ◽  
E. Frau ◽  
...  

Herpetic retinitis in humans is characterized by a high frequency of bilateral localization. In order to determine the possible mechanisms leading to bilateral retinitis, we studied the pathways by which herpes simplex virus type 1 (HSV-1) is propagated from one retina to the other after intravitreal injection in mice. HSV-1 strain SC16 (90 p.f.u.) was injected into the vitreous body of the left eye of BALB/c mice. Animals were sacrificed 1, 2, 3, 4 and 5 days post-inoculation (p.i.). Histological sections were studied by immunochemical staining. Primary retinitis in the inoculated eye (beginning 1 day p.i.) was followed by contralateral retinitis (in the uninoculated eye) starting at 3 days p.i. Infected neurons of central visual pathway nuclei (lateral geniculate nuclei, suprachiasmatic nuclei and pretectal areas) were detected at 4 days p.i. Iris and ciliary body infection was minimal early on, but became extensive thereafter and was accompanied by the infection of connected sympathetic and parasympathetic pathways. The pattern of virus propagation over time suggests that the onset of contralateral retinitis was mediated by local (non-synaptic) transfer in the optic chiasm from infected to uninfected axons of the optic nerves. Later, retinopetal transneuronal propagation of the virus from visual pathways may have contributed to increase the severity of contralateral retinitis.


1996 ◽  
Vol 40 (4) ◽  
pp. 846-851 ◽  
Author(s):  
A M Thackray ◽  
H J Field

The effects of famciclovir (FCV) and valaciclovir (VACV) were compared in a cutaneous infection model for herpes simplex virus type 2 (HSV-2). The compounds were administered orally from day 1 to day 5 postinfection. Both compounds reduced local inflammation and virus replication in the skin. FCV markedly reduced mortality and virus replication in the nervous system. On the cessation of therapy after 5 days, when the levels of infectious virus in the tissues were reduced to below the level of detection, there followed a rebound of virus replication in the ganglia and brain stems of mice that had been treated with VACV. The recurrence of infection in the brain stem occurred on three separate occasions. No such recurrences were observed following FCV treatment. When ganglia were explanted from survivors 6 weeks later, latent virus was shown to be reactivated in all 10 of 10 control, untreated mice. The number of mice whose ganglia yielded virus was reduced to 60% in mice that had been treated with VACV, whereas no mice that had been treated with FCV had evidence of latent infection by this test.


1995 ◽  
Vol 58 (10) ◽  
pp. 1150-1152 ◽  
Author(s):  
D. BARDELL

Droplets of saliva containing herpes simplex virus type 1 were placed on latex disposable gloves. The temperature at the surface of the gloved hand was 34°C. There was no loss of infectious virus before 15 min. Between 15 and 30 min there was a 2-log-cycle drop in titer, and infectious virus could still be recovered after 1 h, the longest period tested. The drop in titer was due to drying of the saliva, which occurred at approximately 21 min. Infectious virus was transferred by touch to lettuce and ham at 0 min when the virus-containing droplets were in a liquid condition, and after 30 and 60 min when the droplets were dry.


2009 ◽  
Vol 90 (8) ◽  
pp. 1937-1942 ◽  
Author(s):  
Subhajit Biswas ◽  
Ricardo Núñez Miguel ◽  
Soumi Sukla ◽  
Hugh J. Field

A variant was selected from a clinical isolate of herpes simplex virus type 1 (HSV-1) during a single passage in the presence of a helicase–primase inhibitor (HPI) at eight times the IC50. The variant was approximately 40-fold resistant to the HPI BAY 57-1293 and it showed significantly reduced growth in tissue culture with a concomitant reduction in virulence in a murine infection model. The variant contained a single mutation (Asn342Lys) in the UL5 predicted functional helicase motif IV. The Asn342Lys mutation was transferred to a laboratory strain, PDK cl-1, and the recombinant acquired the expected resistance and reduced growth characteristics. Comparative modelling and docking studies predicted the Asn342 position to be physically distant from the HPI interaction pocket formed by UL5 and UL52 (primase). We suggest that this mutation results in steric/allosteric modification of the HPI-binding pocket, conferring an indirect resistance to the HPI. Slower growth and moderately reduced virulence suggest that this mutation might also interfere with the helicase–primase activity.


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