1: Ann Rheum Dis. 2008 May 26. [Epub ahead of print]

Risk factors for major infections in Wegener's franulomatosis: analysis of 113
patients.

Charlier C, Henegar C, Launay O, Pagnoux C, Berezne A, Bienvenu B, Cohen P,
Mouthon L, Guillevin L.

Assistance Publique - Hôpitaux de Paris, Hôpital Cochin, France.

OBJECTIVE: To characterize major infectious complications and analyze potential
risk factors in Wegener's granulomatosis (WG) patients. METHODS: Data from 113 WG
patients (69 men) followed at least once between January 1984 and March 2006 in
our internal medicine department were analyzed retrospectively. RESULTS: Thirty
five patients (mean age at WG diagnosis: 50.2 (+/-13.05) years) developed 53
major infections. Infections were: bronchopneumonias (n = 19), herpes zoster
recurrences (n = 9), cellulitis (n = 4), prostatitis (n = 4), spondylodiscitis
and septic arthritis (n = 3), digestive tract infections (n = 2), Enterococcus
faecalis or Staphylococcus aureus septicemia (n = 2), viral hepatitis B
reactivations (n = 2), post-transfusion HIV infection with fatal cerebral
toxoplasmosis, esophageal candidiasis, disseminated herpes simplex and
cytomegalovirus infection, cytomegalovirus retinitis, herpetic keratitis,
herpetic stomatitis, Serratia sp. node suppuration and fever resolving under
broad spectrum antibiotics (n = 1 each). Half of the major infectious episodes
occurred within the 3 years after WG diagnosis. Eight (7%) patients died, with
two (2%) infection-related deaths. Patients diagnosed with WG before 1996 had a
significantly higher rate of infections than those diagnosed later (48% vs. 24%, 
p = 0.02). Cyclophosphamide and corticosteroids were independently associated
with significantly higher risk of major infection (p<0.05 and <0.001
respectively). All patients treated since 1993 received anti-pneumocystosis
prophylaxis. CONCLUSION: Cyclophosphamide and corticosteroids were associated
with higher risk of infection. Despite systematic cotrimoxazole prophylaxis,
major infections, mostly bronchopneumonias and herpes zoster recurrences, were
still common in the course of WG.

PMID: 18504289 [PubMed - as supplied by publisher]

2: Jpn J Infect Dis. 2008 May;61(3):205-9.

Immune Reconstitution Inflammatory Syndrome among HIV/AIDS Patients during Highly
Active Antiretroviral Therapy in Addis Ababa, Ethiopia.

Huruy K, Mulu A, Mengistu G, Shewa-Amare A, Akalu A, Kassu A, Andargie G, Elias
D, Torben W.

Department of Medical Laboratory Technology, College of Medicine and Health
Sciences, University of Gondar, Gondar, Ethiopia. kasaye88@yahoo.com.

Suppression of viral replication is followed by increases in CD4+ lymphocytes,
and this has been shown to result in decreased susceptibility to opportunists
after initiation of highly active antiretroviral therapy (HAART). However,
clinical aggravations after the initiation of HAART have been thought to be due
to the restored ability to mount an inflammatory response, or the immune
reconstitution inflammatory syndrome (IRIS). The degree of IRIS observed in human
immunodeficiency virus (HIV)-infected patients following initiation of HAART is
variable. This prospective study was aimed at determining the proportion of IRIS 
and the pattern of opportunistic infections among 186 HIV/AIDS patients receiving
HAART between December 2006 and July 2007 at Zewditu Memorial Hospital, Addis
Ababa, Ethiopia. The proportion of IRIS was 17.2% (32/186). The mean number of
days of IRIS occurrence for each disease ranged from 26 to 122 days with a mean
of 80. Opportunistic diseases associated with IRIS were tuberculosis (68.8%,
22/32), herpes zoster rash (12.5%, 4/32), cryptococcosis (9.4%, 3/32),
toxoplasmosis (6.3%, 2/32) and bacterial pneumonia (3.1%, 1/32). Compared to
baseline readings there were significant increases in CD4 count, aspartate
aminotransferase and alanine aminotransferase levels while hemoglobin values
decreased during the development of IRIS. In summary, the proportion of IRIS and 
the pattern of opportunistic infections in HAART-treated patients in Ethiopia
mirrored those reported in other countries. Further prospective surveys on
epidemiological, immunological, microbial and clinical studies are imperative to 
assess the proportion and pattern of IRIS and effect of HAART in Ethiopia.

PMID: 18503170 [PubMed - in process]

3: Medicina (B Aires). 2008;68(2):125-8.

[Clinical and epidemiological aspects of herpes zoster]

[Article in Spanish]

Vujacich C, Poggi E, Cecchini D, Luchetti P, Stamboulian D.

Fundación del Centro de Estudios Infectológicos, Buenos Aires, Argentina.
cvujacich@funcei.org.ar

Herpes zoster (HZ) is a public health problem worldwide. Although, there is
paucity of data of this disease from South American countries. The objective of
this study was to evaluate clinical and epidemiological aspects of HZ in a
population of patients from South America. We underwent a retrospective analysis 
of clinical charts of an infectious diseases reference center (period:
2000-2005). Univariate analysis was performed to assess variables related to post
herpetic neuralgia (PHN). From a total of 302 cases, 62% were in women. The
median age was 57 years: 16.1% of the patients had a predisposing condition for
the development of HZ. Most frequent dermatomes involved were: thoracic,
ophthalmic and lumbar; 93.5% of the patients received antiviral drugs and 94%
complementary medications. The most frequent complication was PHN and was related
with age over 50 years. Clinical and epidemiological aspects of HZ and the
frequency of complications in our population were similar to data from developed 
countries.

Publication Types: 
    English Abstract

PMID: 18499960 [PubMed - in process]

4: An Sist Sanit Navar. 2008 Jan-Apr;31(1):71-80.

[Varicella and herpes zoster incidence prior to the introduction of systematic
child vaccination in Navarre, 2005-2006.]

[Article in Spanish]

García Cenoz M, Castilla J, Montes Y, Morán J, Salaberri A, Elía F, Floristán Y, 
Rodrígo I, Irisarri F, Arriazu M, Zabala A, Barricarte A.

Instituto de Salud Pública de Navarra, 31003, Pamplona, Spain.
mgcenoz@cfnavarra.es.

Varicella is an acute and highly contagious disease produced by the
varicella-zoster virus, which leaves lasting immunity. Herpes zoster is produced 
by reactivation of a latent infection of the same virus. The introduction of
systematic and free vaccination against varicella in children of 15 months in
Navarre from 2007 onwards can be expected to produce important epidemiological
changes. For this reason we describe the previous epidemiological situation in
the period from 2005 to 2006. We analysed all cases of varicella and herpes
zoster registered in the electronic clinical files of primary care, in the
database of hospital discharges and in the mortality register. Between 2005 and
2006, 9,908 cases of varicella were diagnosed (8.29 annually per 1,000
inhabitants), with 90% in children under 15 years old. There were 80 hospital
admissions (8 for every 1,000 cases), complications in 2.5 out of every 1,000
cases, and there was one death due to this cause (0.1 per 1,000 cases). In the
same period, 4,959 cases of herpes zoster were diagnosed (4.15 cases per 1,000
inhabitants), half in people over 55 years old. There were 179 hospital
admissions (36 per 1,000 cases), whose average age was 77, and 83 presented
complications (16.7 per 1,000 cases). This epidemiological pattern is similar to 
that found in other places before the introduction of the vaccine.

Publication Types: 
    English Abstract

PMID: 18496581 [PubMed - in process]

5: J Virol. 2008 May 21. [Epub ahead of print]

Herpes simplex virus type 1 ICP27 regulates expression of a variant, secreted
form of glycoprotein C by an intron-retention mechanism.

Sedlackova L, Perkins KD, Lengyel J, Strain AK, van Santen VL, Rice SA.

Department of Microbiology, University of Minnesota Medical School, Minneapolis, 
MN 55455; and Department of Pathobiology, 264 Greene Hall, College of Veterinary 
Medicine, Auburn University, Auburn, Alabama 36849-5519.

We previously showed that herpes simplex virus type 1 (HSV-1) immediate-early
(IE) protein ICP27 can post-transcriptionally stimulate mRNA accumulation from a 
transfected viral late gene encoding glycoprotein C (gC) (Perkins, K.D., J.
Gregonis, S. Borge, and S.A. Rice, J. Virol. 77:9872-9884, 2003). We began this
study by asking whether ICP27 homologs from other herpesviruses can also mediate 
this activity. Although the homologs from varicella-zoster virus (VZV) and human 
cytomegalovirus (HCMV) were inactive, the homolog from bovine herpesvirus 4
(BHV-4), termed HORF1/2, was a very efficient transactivator. Surprisingly, most 
of the mRNA produced via HORF1/2 transactivation was 225 nucleotides shorter than
expected due to the removal of a previously undescribed intron from the gC
transcript. We found that the gC mRNA produced in the absence of transactivation 
was also mostly spliced. In contrast, gC mRNA produced by ICP27 transactivation
was predominantly unspliced. Based on these results, we conclude that ICP27 has
two distinct effects on the transfected gC gene: it i) stimulates mRNA
accumulation, and ii) promotes the retention of an intron. Interestingly, the
spliced transcript encodes a variant of gC that lacks its transmembrane domain
and is secreted from transfected cells. As the gC splicing signals are conserved 
amongst several HSV-1 strains, we investigated whether the variant gC is
expressed during viral infection. We report here that both the spliced transcript
and its encoded protein are readily detected in Vero cells infected with three
different laboratory strains of wild-type HSV-1. Moreover, the variant gC is
efficiently secreted from infected cells. We have designated this alternate form 
of the protein as gCsec. As the extracellular domain of gC is known to bind
heparan sulphate (HS)-containing proteoglycans and to inhibit the complement
cascade via an interaction with complement component C3b, we speculate that gCsec
could function as a secreted virulence factor.

PMID: 18495765 [PubMed - as supplied by publisher]

6: Clin Infect Dis. 2008 May 20. [Epub ahead of print]

Tularemia with Vesicular Skin Lesions May Be Mistaken for Infection with Herpes
Viruses.

Byington CL, Bender JM, Ampofo K, Pavia AT, Korgenski K, Daly J, Christenson JC, 
Adderson E.

1Department of Pediatrics, University of Utah, and 2Primary Children’s Medical
Center, Salt Lake City, Utah; 3Department of Pediatrics, Indiana University,
Indianapolis; and 4Department of Pediatrics, St. Jude’s Children’s Research
Hospital, Memphis, Tennessee.

The original reports of human infection with Francisella tularensis noted
vesicular skin rash as a manifestation. We present 2 cases of tularemia initially
diagnosed as herpes simplex or varicella zoster infection. Clinicians must
recognize the cutaneous manifestations of tularemia and be able to distinguish
these from lesions seen with herpes viruses.

PMID: 18491968 [PubMed - as supplied by publisher]

7: Arch Dermatol. 2008 May;144(5):603-8.

Family history as a risk factor for herpes zoster: a case-control study.

Hicks LD, Cook-Norris RH, Mendoza N, Madkan V, Arora A, Tyring SK.

University of Texas Medical School at Houston, USA. Lindsey.D.Hicks@uth.tmc.edu

OBJECTIVE: To assess risk factors for herpes zoster beyond age and
immunosuppression, especially the association with a family history of herpes
zoster, since a preventative herpes zoster and postherpetic neuralgia vaccine is 
now available. DESIGN: We undertook a case-control study of herpes zoster, which 
represents reactivation of latent varicella zoster virus residing in dorsal root 
ganglia following primary infection, involving 504 patients and 523 controls.
Interviews were conducted by trained medical investigators using a structured
questionnaire. SETTING: The Center for Clinical Studies, an outpatient clinic and
research center in Houston, Texas. PARTICIPANTS: Nonimmunocompromised patients
with confirmed cases of herpes zoster were included in the study. Controls were
nonimmunocompromised clinic patients with new diagnoses of skin diseases other
than herpes zoster. RESULTS: Cases were more likely to report blood relatives
with a history of zoster (39%) compared with controls (11%; P < .001). Risk was
increased with multiple blood relatives (odds ratio, 13.77; 95% confidence
interval, 5.85-32.39) compared with single blood relatives (odds ratio, 4.50; 95%
confidence interval, 3.15-6.41). CONCLUSIONS: The results suggest an association 
between herpes zoster and family history of zoster. Future studies will be needed
to investigate this association.

PMID: 18490586 [PubMed - in process]

8: Mol Gen Mikrobiol Virusol. 2008;(2):37-41.

[Mutational pressure in genomes of alphaherpesviruses infecting human]

[Article in Russian]

[No authors listed]

Genomes of the herpes simplex viruses are extremely enriched with GC. Elevated
G+C level in genomes of the simplex viruses is a result of their long-term
evolution under the influence of the mutational pressure. We counted the rates of
nucleotide substitutions from gene coding major capsid protein (MCP) (G+C = 0.68,
3GC = 0.89) of human simplex virus 1 (HSV-1) to the MCP gene (G+C = 0.70, 3GC =
0.91) of HSV-2 (the first pair of genes) and from the same MCP gene of HSV-1 to
the homologous gene (G+C = 0.73, 3GC = 0.99) from cercopithecine herpes virus 16 
(the second pair of genes). The rates of transitions from A-T to G-C base pairs
increases 2.17-, 3.09-, and 1.27-fold in the first, second, and third codon
positions, respectively, if compared those rates between the second and first
pair of genes (the growth of GC-richness is only 3%). This effect is due to an
approximately 90% GC-richness of the third codon positions in all those genes.
Transitions caused by the strong mutational pressure (from A-T to G-C base pairs)
have a low probability to occur in the third positions, but high probability to
occur in the first and second positions. For MCP gene of human herpes 3, the
probability of the occurrence of transition caused by mutational pressure in the 
third codon position is 2.36 times higher than in MCP gene of HSV1, and 3 times
higher than in MCP gene of HSV2. These data could provide an explanation of
rarely occurring relapses of herpes Zoster infection and frequently occurring
relapses of herpes simplex infection.

Publication Types: 
    English Abstract

PMID: 18488448 [PubMed - in process]

9: Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1277-81.

Long-term Anti-inflammatory and Antihistamine Medication Use and Adult Glioma
Risk.

Scheurer ME, El-Zein R, Thompson PA, Aldape KD, Levin VA, Gilbert MR, Weinberg
JS, Bondy ML.

Department of Epidemiology, University of Texas M. D. Anderson Cancer Center,
Unit 1340, P.O. Box 301439, Houston, TX 77230-1439. mbondy@mdanderson.org.

A personal history of asthma or allergy has been associated with a reduced risk
for adult malignant gliomas. Recent reports on the use of nonsteroidal
anti-inflammatory drugs (NSAID) and the presence of risk alleles in asthma
susceptibility genes showed similar inverse associations. To further explore the 
relationship between immune mediators and gliomas, we examined the use of NSAID
and antihistamines, history of asthma or allergy, and infection in 325 glioma
cases and 600 frequency-matched controls from the metropolitan area of Houston,
TX (2001-2006). The regular use of NSAID was associated with a 33% reduction in
the risk for glioma, suggestive of possible antitumor activity. Surprisingly,
regular long-term antihistamine use among those reporting a history of asthma or 
allergies was significantly associated with a 3.5-fold increase in the risk for
glioma. Similar to previous reports, cases in our study were less likely to have 
reported asthma, allergy, or a history of a number of viral infections
(chickenpox or shingles, oral herpes, and mononucleosis) than controls. We
therefore speculate that the observed positive association with antihistamine use
may reflect an alteration of protective immune factors in susceptible
individuals. Our results lend additional support for an important but unknown
link between malignant brain tumors and immune mediators. (Cancer Epidemiol
Biomarkers Prev 2008;17(5):1277-81).

PMID: 18483351 [PubMed - in process]

10: Spec Care Dentist. 2000 Nov-Dec;20(6):245-9.

The issues and challenges of orofacial pain in the elderly.

Cox MO.

University of Colorado School of Dentistry, USA.

Dental pain is among the most prevalent of all pain complaints, and pain is
frequently given as a common reason for both avoiding and seeking dental care.
Pain is frequently an essential component in the differential diagnosis of many
diseases; however, in the elderly, diagnosis is more difficult due to a greater
frequency of multiple chronic diseases and an altered pain response. It is
important to understand the nature and prevalence of pain in this group, and one 
should be cautious to avoid the oversimplification that "pain decreases with
age." Current studies involving the differences in assessing pain and therapeutic
pain control between younger and older age groups are discussed. Pain prevalence 
is discussed along with herpes zoster, post-herpetic neuralgia, fibromyalgia,
toothache pain, burning mouth syndrome, and trigeminal neuralgia as they relate
to the elderly. Pain assessment can be made by means of pain scales and specific 
open- and closed-ended questions. There is evidence that some practitioners may
be underestimating the severity of pain in the elderly, and thus not prescribing 
adequate analgesics when indicated. When analgesics are prescribed, a thorough
analysis of the patients' current medications and condition should lead to a
customized prescription and dosage.

PMID: 18481416 [PubMed - in process]

11: Int J Dermatol. 2008 Jun;47(6):640-1.

Herpes zoster after varicella vaccination in a healthy young child.

Obieta MP, Jacinto SS.

Publication Types: 
    Letter

PMID: 18477170 [PubMed - in process]

12: Nephrology (Carlton). 2008 Jun;13(4):331-6.

Efficacy of enteric-coated mycophenolate sodium in patients with active lupus
nephritis.

Mak SK, Lo KY, Lo MW, Chan SF, Tong GM, Wong PN, Wong AK.

Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, Kowloon,
Hong Kong. maksk@ha.org.hk

BACKGROUND: The ideal treatment of lupus nephritis has yet to be defined. Both
cyclophosphamide and mycophenolate mofetil have been used with encouraging
results, but adverse events are frequently seen. There are no data on the use of 
enteric-coated mycophenolate sodium. METHODS: We retrospectively reviewed 12
patients with active forms of lupus nephritis (1 class III, 7 class IV and 4
class V) treated with enteric-coated mycophenolate sodium combined with
corticosteroids. RESULTS: The mean age of the patients was 32.3 +/- 11.2 years
and the average length of follow up was 25.9 +/- 8.9 months. The mean serum
creatinine clearance was 93 +/- 30.1 mL/min per 1.73 m(2) and the mean
proteinuria level was 4.5 +/- 3.6 g/day. All had features that warranted
aggressive treatment. Mycophenolate sodium was given for 12.9 +/- 9.7 months with
an averaged starting dose of 1350 +/- 163 mg/day. Six patients attained complete 
remission and six attained partial remission with treatment. The mean interval to
attain first remission (complete or partial) was 8.3 +/- 5.7 weeks. At last
follow up, all patients were in complete or partial remission. Apart from herpes 
zoster that developed in one patient, no other significant side-effects were
encountered. CONCLUSION: Enteric-coated mycophenolate sodium was effective and
well-tolerated in the treatment of active lupus nephritis.

PMID: 18476916 [PubMed - in process]

13: Ther Clin Risk Manag. 2007 Aug;3(4):633-9.

Prevention of shingles: safety and efficacy of live zoster vaccine.

Quan D, Cohrs RJ, Mahalingam R, Gilden DH.

Primary infection with varicella zoster virus (VZV) causes chickenpox (varicella)
after which virus becomes latent in cranial nerve, dorsal root and autonomic
ganglia along the entire neuraxis. Virus may later reactivate, causing shingles
(zoster), characterized by pain and rash restricted to 1-3 dermatomes. More than 
40% of zoster patients over age 60 develop postherpetic neuralgia (PHN), pain
that persists for months to years. The socioeconomic impact of primary varicella 
infection has been lessened by introduction of VZV vaccine for children. However,
the effect of childhood vaccination on the incidence of zoster is unknown. Virus 
reactivation correlates with waning cell-mediated immunity (CMI) to VZV with
normal aging. Adults exposed to children with varicella may have a boost in CMI
to VZV. For at least several more decades, the incidence of zoster may increase
as the elderly population grows. The anticipated increase in zoster burden of
illness in future decades was a major impetus for the Shingles Prevention Study, 
a prospective, double-blind, placebo-controlled trial of attenuated VZV vaccine
to prevent zoster in older adults. This review discusses clinical and virological
aspects of zoster and its complications, current treatment options, and VZV
vaccine development along with its future role in disease prevention.

PMID: 18472986 [PubMed - in process]

14: Virology. 2008 May 7. [Epub ahead of print]

Plasma membrane cholesterol is required for efficient pseudorabies virus entry.

Desplanques AS, Nauwynck HJ, Vercauteren D, Geens T, Favoreel HW.

Department of Virology, Parasitology and Immunology, Faculty of Veterinary
Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.

Alphaherpesviruses comprise closely related viruses of man and animal, including 
herpes simplex virus, varicella-zoster virus and pseudorabies virus (PRV). Here, 
using methyl-beta-cyclodextrin and fluorescently tagged PRV, we directly show
that depletion of cholesterol from the plasma membrane of host cells
significantly reduces PRV entry. Cholesterol depletion did not reduce PRV
attachment, but stalled virus particles at the plasma membrane before penetration
of the cell. Cholesterol depletion results in destabilization of lipid raft
microdomains in the plasma membrane, which have been shown before to be involved 
in efficient entry of different viruses. A significant fraction of PRV virions
appears to localize juxtaposed to GM1, a lipid raft marker, during entry.
Together, these data indicate that cholesterol and possibly cholesterol-rich
lipid rafts may be important during PRV entry.

PMID: 18471850 [PubMed - as supplied by publisher]

15: Epidemiol Infect. 2008 May 9:1-10. [Epub ahead of print]

Epidemiology and cost of herpes zoster and post-herpetic neuralgia in the United 
Kingdom.

Gauthier A, Breuer J, Carrington D, Martin M, Rémy V.

i3 Innovus, Uxbridge, Middlesex, UK.

SUMMARYRecent information on epidemiology and management of herpes zoster (HZ)
and post-herpetic neuralgia (PHN), a painful complication of HZ, is scarce. The
objective of this study was to document the burden of HZ and PHN in the United
Kingdom. This retrospective analysis of the UK General Practice Research Database
aimed to estimate HZ incidence and proportion of HZ patients developing PHN and
to assess management costs in immunocompetent individuals aged 50 years. A cohort
of 27 225 HZ patients was selected, corresponding to an incidence of 5.23/1000
person-years. Respectively 19.5% and 13.7% of patients developed PHN at least 1
and 3 months after HZ diagnosis. Mean direct cost was pound103 per HZ patient and
pound341 and pound397 per PHN episode (1- and 3-month definition respectively).
Both HZ and PHN costs increased markedly with pain severity. This study confirms 
that HZ and PHN are frequent and costly diseases in the United Kingdom.

PMID: 18466661 [PubMed - as supplied by publisher]

16: Infection. 2008 May 3. [Epub ahead of print]

Diabetes as a Risk Factor for Herpes Zoster Infection: Results of a
Population-Based Study in Israel.

Heymann AD, Chodick G, Karpati T, Kamer L, Kremer E, Green MS, Kokia E, Shalev V.

Medical Division, Maccabi Healthcare Services, 27 HaMered St, Tel Aviv, 68125,
Israel.

BACKGROUND: Studies showed that diabetes mellitus (DM) is often accompanied by
impaired cell-mediated immunity, which potentially may increase the risk for
infectious diseases, including herpes zoster (HZ). However, data on the relation 
between DM and HZ are scarce. This case-control study explored the association
between DM and HZ. PATIENTS AND METHODS: This study was nested within a cohort of
all members of a large health maintenance organization (HMO) in Israel. Cases
totaled 22,294 members who were diagnosed with HZ between 2002 and 2006. Controls
(n = 88,895) were randomly selected from the remaining HMO population using
frequency-matched age, sex, and duration of follow-up. Personal data on history
of DM, lymphoma, leukemia, or AIDS, were obtained from computerized medical
records. RESULTS: Adjusted analyses showed that the risk of HZ was associated
with history of leukemia, lymphoma, use of steroids or antineoplastic
medications, and AIDS, particularly among patients below 45 years of age. In a
multivariate analysis, DM was associated with an increased risk of HZ (OR = 1.53;
95% CI: 1.44-1.62). CONCLUSIONS: The data suggest that individuals with DM are at
increased risk of HZ. Well-designed cohort studies may help to clarify the nature
of this association.

PMID: 18454342 [PubMed - as supplied by publisher]

17: J Infect Dis. 2008 Mar 1;197 Suppl 2:S61-5.

A model of lytic, latent, and reactivating varicella-zoster virus infections in
isolated enteric neurons.

Gershon AA, Chen J, Gershon MD.

Department of Pediatrics, Columbia University College of Physicians and Surgeons,
New York, New York 10032, USA. aag1@columbia.Edu

Because human primary afferent neurons are not readily obtained, we sought to
develop a model in which the lytic, latent, and reactivating phases of
varicella-zoster virus (VZV) infection were recapitulated in neurons from an
animal source. Enteric neurons were obtained from the small intestine of adult
guinea pigs and from the bowel of fetal mice. Latency was established when these 
neurons were infected by cell-free VZV in the absence of fibroblasts or other
cells of mesodermal origin. In contrast, lytic infection ensued when fibroblasts 
were present or when the enteric neurons were infected by cell-associated VZV.
Latency was associated with the expression of a limited subset of viral genes,
the products of which were restricted to the cytoplasm. Lysis was associated with
the expression of viral glycoproteins, nuclear translocation of
latency-associated gene products, and rapid cell death. Reactivation was
accomplished by expressing VZV open reading frame (ORF) 61p or herpes simplex
virus ICP0 in latently infected neurons. Isolated enteric neurons from guinea
pigs and mice recapitulate latent gene expression in human cranial nerve and
dorsal root ganglia. Expression of latency-associated VZV gene products was
detected in 88% of samples of adult human intestine, suggesting that VZV not only
infects enteric neurons but also is latent in the human enteric nervous system.
This in vitro model should facilitate further understanding of latency and
reactivation of VZV.

Publication Types: 
    Evaluation Studies
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18419411 [PubMed - indexed for MEDLINE]

18: J Infect Dis. 2008 Mar 1;197 Suppl 2:S58-60.

Humoral and cellular immunity to varicella-zoster virus: an overview.

Arvin AM.

Department of Pediatrics, Stanford University School of Medicine, Stanford,
California 94305, USA. aarvin@stanford.edu

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18419410 [PubMed - indexed for MEDLINE]

19: J Infect Dis. 2008 Mar 1;197 Suppl 2:S54-7.

Vaccine Oka variants and sequence variability in vaccine-related skin lesions.

Breuer J, Schmid DS.

Skin Virus Laboratory, Centre for Cutaneous Research, St. Bartholomew's and The
Royal London School of Medicine and Dentistry, Queen Mary College, London, United
Kingdom.

As with most live attenuated viral vaccines, varicella vaccine comprises a
mixture of variant strains. Knowledge about the pathogenic potential of
individual strains in the varicella vaccine is limited. Vaccination against
chickenpox causes a usually modified varicella-like rash in a small percentage of
healthy children, and vaccine virus reactivates on rare occasions to cause herpes
zoster (HZ). In several published studies, our respective laboratories have
analyzed genomic variation among specimens from cases of postvaccination rash and
HZ in vaccine recipients, focusing on polymorphisms between vaccine Oka strains
and the parental Oka strain. In most respects, these studies were in close
agreement, identifying the set of wild-type markers among vaccine adverse event
isolates, each occurring at similar frequencies. The same 3 universally present
vaccine markers, at positions 106262, 107252, and 108111, were also identified by
both laboratories. One notable difference has been the observation of mostly
clonal vaccine virus among isolates examined by one laboratory and mostly mixed
viruses in isolates examined by the other. In addition to reviewing and comparing
our combined observations, we propose possible explanations for our contrasting
findings and propose future studies to reconcile them.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18419409 [PubMed - indexed for MEDLINE]

20: J Infect Dis. 2008 Mar 1;197 Suppl 2:S41-4.

Development of varicella vaccine.

Takahashi M, Asano Y, Kamiya H, Baba K, Ozaki T, Otsuka T, Yamanishi K.

Department of Virology, Research Institute for Microbial Diseases, Osaka
University, Suita, Osaka, Japan. mtakahashi@mail.biken.or.jp

The Oka strain of varicella-zoster virus (VZV) was first isolated from vesicles
of an otherwise healthy 3-year-old boy with typical varicella. The virus was
passaged 11 times in human embryonic lung fibroblasts at 34 degrees C and 12
times in guinea pig embryo fibroblasts (GPEFs) at 37 degrees C. GPEFs were the
only nonprimate cells tested in which some degree of viral replication occurred. 
The resultant virus was temperature sensitive and showed host dependency,
measured as better replication in GPEFs than that shown by the parental virus.
The passaged virus was used as a candidate varicella vaccine and proved safe and 
effective for healthy and immunocompromised children. During the follow-up of
vaccinated children with acute lymphocytic leukemia, the incidence of herpes
zoster (HZ) was significantly lower among children who did not have a rash after 
vaccination, compared with those who had a rash caused by VZV (6 [2.3%] of 260
vs. 12 [17.1%] of 70, respectively). Because of the pathogenesis of VZV, the
incidence of latency and of HZ is predicted to be lower among vaccine recipients 
than among individuals who have experienced varicella.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18419406 [PubMed - indexed for MEDLINE]