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Analysis of herpes simplex virus type 1 restriction fragment length polymorphism variants associated with herpes gladiatorum and Kaposi's varicelliform eruption in sumo wrestlers


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The geographical distribution of herpes simplex virus type 1 (HSV-1) restriction fragment length polymorphism (RFLP) variants BgK(L) and BgO(L) and the high relative frequency (RF) of BgK(L) in orolabial lesions has led to a dispersion-replacement hypothesis for these variants. The pathogenic properties of HSV-1 variants in mice and professional sumo wrestlers were examined here. The wrestlers herpes gladiatorum (HG) was caused by primary and non-primary HSV-1 infections and recurred in many wrestlers. HSV-1 neutralizing antibody titres in sera from wrestlers who did not develop HG were relatively high. HG was caused by distinct HSV-1 variants and strains from wrestlers living in the same sumo stable. The BgK(L) RF was significantly higher in HG cases, particularly in those with Kaposi's varicelliform eruption. These data indicated that reactivation and transmission of latent HSV-1 infections, especially BgK(L), occurred frequently among wrestlers and was caused by severe skin damage. These results support the BgK(L) dispersion hypothesis.
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Analysis of herpes simplex virus type 1 restriction
fragment length polymorphism variants associated
with herpes gladiatorum and Kaposi’s varicelliform
eruption in sumo wrestlers
Fumihiko Ban,
Satoe Asano,
Shigeru Ozawa,
Hiroyuki Eda,
James Norman,
William G. Stroop
and Kazuo Yanagi
Kazuo Yanagi
Herpesvirus Laboratory, Department of Virology I, National Institute of Infectious Diseases, Toyama
1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
BML General Institute, Matoba 1361-1, Kawagoe, Saitama 350-1101, Japan
Department of Dermatology, Doai Kinen Hospital (Fraternity Memorial Hospital, Japan), Yokoami
2-1-11 Sumida-ku, Tokyo 130-8587, Japan
Yamanashi Institute of Health, Kofu City, Yamanashi Prefecture, Japan
Department of Ophthalmology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-
3498, USA
Received 21 April 2008
Accepted 10 June 2008
The geographical distribution of herpes simplex virus type 1 (HSV-1) restriction fragment length
polymorphism (RFLP) variants BgK
and BgO
and the high relative frequency (RF) of BgK
orolabial lesions has led to a dispersion–replacement hypothesis for these variants. The
pathogenic properties of HSV-1 variants in mice and professional sumo wrestlers were examined
here. The wrestlers herpes gladiatorum (HG) was caused by primary and non-primary HSV-1
infections and recurred in many wrestlers. HSV-1 neutralizing antibody titres in sera from wrestlers
who did not develop HG were relatively high. HG was caused by distinct HSV-1 variants and
strains from wrestlers living in the same sumo stable. The BgK
RF was significantly higher in HG
cases, particularly in those with Kaposi’s varicelliform eruption. These data indicated that
reactivation and transmission of latent HSV-1 infections, especially BgK
, occurred frequently
among wrestlers and was caused by severe skin damage. These results support the BgK
dispersion hypothesis.
Herpes simplex virus type 1 (HSV-1) variant BgK
is a
restriction fragment length polymorphism (RFLP) variant
(Ozawa et al., 1988, 1989a) caused by loss of the BglII
cleavage site between the BglII K and Q/13 fragments (Eda
et al., 2007). BgK
is a good surrogate marker for the HSV-
1 multiple mutant BgK
where SaCFJ
denotes loss of SalI fragments C, F and J,
denotes a larger SalI L fragment, SaGH
denotes loss
of SalI G and H fragments and KpM
denotes a smaller
KpnI M fragment (Eda et al., 2007; Ozawa et al., 2006). The
prevalence of BgK
in HSV-1 clinical isolates, referred to as
its relative frequency (RF), is 27 % in Japan (Ozawa et al.,
2006). Another HSV-1 RFLP variant BgO
(Ozawa et al.,
1989b) has lost the BglII cleavage site between the BglII Q/
13 and O fragments (Eda et al., 2007). It has been proposed
that BgK
spread and replaced BgO
in Japan, based on the
geographical distribution profiles of BgK
and BgO
et al., 2007; Ozawa et al., 1989b, 2006) and the high RF of
in orolabial infections (Ozawa et al., 2007).
In the present study, we compared the pathogenic and
epidemiological properties of HSV-1 BgK
, BgO
and non-
variants in mice and sumo wrestlers with
herpes gladiatorum (HG). Central nervous system (CNS)
destruction is a major consequence of experimental murine
disease induced by HSV-1 (Dix et al., 1983b; Goel et al.,
2002; Mao & Rosenthal, 2003; Richards et al., 1981;
Roizman & Knipe, 2001). HG has been documented
among wrestlers and rugby players (Anderson, 2003;
Becker, 1992; Belongia et al., 1991; De Bernardo, 1992;
Turbeville et al., 2006; White & Grant-Kels, 1984). HSV-1
isolates from HG cases in professional sumo wrestlers that
3Present address: St Louis Laboratories, Pfizer Inc., 700 Chesterfield
Parkway West, Mail Zone AA3C Chesterfield, MO 63017, USA.
4Present address: AIDS Research Center National Institute of Infectious
Diseases, Toyama 1-23-1, Shinjuku, Tokyo 162-8640, Japan.
Two supplementary figures and data supplements A–K are available
with the online version of this paper.
Journal of General Virology (2008), 89, 2410–2415 DOI 10.1099/vir.0.2008/003368-0
2410 2008/003368 G2008 SGM Printed in Great Britain
were previously described by Asano et al. (1994) were
analysed further because the high HG frequency in these
wrestlers and their traditional lifestyle, in which they live
together in communal and isolated sumo stables, facilitated
studies of HSV-1 epidemiology.
For pathogenicity experiments in mice, the HSV-1 isolates
(and their isolation sites) used were: BgK
isolates RM48
(skin), TS9 (gingivostomatitis) and KH424 (keratitis);
isolates RM57 (mouth), Y82-469 (mouth) and
IW30 (lips); and non-BgK
isolates RK
[Kaposi’s varicelliform eruption (KVE)], TS5 (lips) and
TS6 (gingivostomatitis). The three non-BgK
isolates showed the same RFLP profiles as strain F (kindly
provided by Dr B. Roizman, University of Chicago) with
BglII, SalI, KpnI, BamHI, HindIII, HpaI and EcoRI (Ozawa
et al., 2006). The pathogenicity of HSV-1 clinical isolates
was assayed (Beers et al., 1993, 1995) by inoculating BALB/
c mice with a dilution series of each virus. Each mouse was
injected with a 20 ml virus suspension for intracranial
inoculations and a 100 ml virus suspension for intraper-
itoneal inoculations. Five mice were injected for each HSV-
1 suspension dilution.
Neuroinvasiveness of the clincial isolates in mice was
examined by intraperitoneal inoculation (Supplementary
Fig. S1a, available in JGV Online) and indicated that the
values were: .6.0 (KH424), 3.2 (RM48) and 4.0
(TS9) for BgK
(i.e. a .2.8 log LD
range); 2.4 (RM57),
4.0 (IW30) and 2.6 (Y82-469) for BgO
(i.e. a 1.6 log LD
range); and 2.6 (RK), 3.0 (TS6) and .6.0 (TS5) for non-
, (i.e. a .3 log LD
range). The neuro-
virulence of the clincial isolates was examined by
intracranial inoculation in mice (Supplementary Fig. S1b)
and indicated that the log
values were: ,1.0
(KH424), ,1.0 (RM48) and 1.8 (TS9) for BgK
(RM57), 1.4 (IW30) and ,1.0 (Y82-469) for BgO
; and
,1.0 (RK), ,1.0 (TS6) and 3.8 (TS5) for non-BgK
(i.e. similar log
values for isolates of the three
variants). These results indicate that the pathogenicity of
isolates in mice, measured as LD
values, varied
widely between isolates and was similar to that for BgO
and non-BgK
isolates and for HSV-1 clinical
isolates (Bergstrom et al., 1990; Dix et al., 1983a, 1983b;
Mao & Rosenthal, 2003; Richards et al., 1981) and mutants
(Roizman & Knipe, 2001).
Clinical specimens and HSV-1 isolates from sumo
wrestlers, described previously by Asano et al. (1994), were
taken between August 1989 and July 1994 from young
professional sumo wrestlers with HG living in eight
different sumo stables in Tokyo: Tomozuna, Takasago,
Oguruma, Nishonoseki, Tatsunami, Kokonoe, Dewanoumi
and Wakamatsu (designated stables B, D, E, G, I, J, K and
L, respectively). Clinical diagnosis was at the Doai Kinen
Hospital (The Fraternity Memorial Hospital). One wrestler
in stable D developed headaches and died 2 months after
clinical diagnosis of HG in 1989 and one wrestler in stable
F was diagnosed with herpes encephalitis in 1990; speci-
mens were not obtained from these two wrestlers, however,
this indicates that HSV-1 infections can be fatal in some
cases and as such they warrant investigation. Specimens
were inoculated into MRC-5 (ATCC, CCL-171) cell
cultures. Thirty-nine sumo wrestlers were diagnosed with
HG; HSV-1 was isolated from 22 of these wrestlers (Asano
et al., 1994) and HSV-2 was isolated from another wrestler
(data not shown). Virus isolates were propagated on Vero
cell (Yasumura & Kawakita, 1988) monolayers and their
HSV type was identified using HSV type-specific mono-
clonal antibodies, with plaque titration performed as
previously described (Yanagi, 1981). The virus suspensions
used in this study were prepared from virus stocks that had
not been passaged more than five times after isolation.
Neutralizing and complement-requiring neutralizing
(CRN) antibodies against HSV-1 in serum specimens were
titrated soon after the specimens were taken, as previously
described (Asano et al., 1994; Yoshino & Abe, 1981;
Yoshino & Isono, 1978). Complement (0.25 units) was
added to each well of 96-well micro-test plates for CRN
antibody titrations (Yoshino & Abe, 1981). RFLP analyses
were performed as previously described (Eda et al., 2007;
Ozawa et al., 2006) using the restriction endonuclease
maps of strain F as references (Hayward et al., 1975; Locker
& Frenkel, 1979; Roizman, 1979; Roizman & Tognon,
Fig. 1. Restriction endonuclease maps of HSV-1 with the
enzymes used in this study. The restriction fragments that showed
polymorphisms in the present report are indicated by large letters.
The asterisks indicate subterminal fragments, the variability of
which was suggested by Roizman & Tognon (1983).
HSV-1 RFLP variants associated with herpes gladiatorum 2411
1983). The terminal internal and ‘joint’ sequences contain-
ing the 280 bp repeat, consisting predominantly of the
terminal reiterated sequence ‘a’ (Davison & Wilkie, 1981;
Locker & Frenkel, 1979; Roizman, 1979) (Fig. 1), were
excluded from the RFLP analyses (Locker & Frenkel, 1979;
Roizman & Tognon, 1983; Wagner & Summers, 1978).
Several subterminal fragments with size variability, as
previously described by Roizman & Tognon (1983), are
indicated in Fig. 1.
In HSV infections, CRN antibody against HSV (Mandel,
1978; Yanagi, 1981; Yoshino et al., 1977; Yoshino & Isono,
1978) appears in early immune sera of infected patients
and experimental animals, as described previously
(Yoshino & Isono, 1978; Yoshino & Taniguchi, 1966;
Zheng & Hsiung, 1984), and CRN antibody titres are
higher than neutralizing antibody titres in early sera
(Yoshino & Isono, 1978; Yoshino & Taniguchi, 1966).
Five sumo wrestler HG cases in stable L presented almost
concurrently (Table 1). One HG case (HG37IY) presented 2
weeks later, another (HG38OH) presented 1 month after
HG37IY and another (HG39OY) presented 8 months after
HG38OH (Table 1). Sera from five HG cases obtained before
or at the onset of HG were negative (i.e. titre ,4) for HSV-
1-neutralizing and CRN antibodies. Four of these cases
seroconverted, as determined by their HSV-1-neutralizing
and CRN antibody titres, but paired sera were not obtained
for the fifth case (HG35HH) (Table 1). These data indicated
that these five HG cases were primary HSV-1 infections. In
three other cases from stable L, the HSV-1-neutralizing and
CRN antibodies were positive before or at HG onset/
diagnosis (Table 1), indicating that these cases were not
primary HSV-1 infections. In four cases from stable E (Table
1), HSV-1-neutralizing and CRN antibodies were negative
in two cases (HG24MT and HG25SM) and positive in two
cases (HG15HK and HG16AT) at the time of HG diagnosis,
indicating that the former cases were primary HSV-1
infections and the latter were not. HG recurred in a number
of sumo wrestlers, as described in data supplement A.
Three wrestlers in stable L did not develop HG despite
living and training together with wrestlers with HG. The
sera of these three wrestlers had HSV-1 neutralizing
antibody titres ¢32 and CRN antibody titres ¢128
(Table 1). These neutralizing antibody levels were higher
than those in sera from wrestlers with HG taken before or
at the onset of HG (Table 1).
Five different HSV-1 isolates with distinct RFLP profiles,
namely different HSV-1 strains, were involved in HG cases
in stable L and two were involved in HG cases in stable D. In
Table 1. HSV-1-neutralizing and CRN antibodies in sera
Case HG diagnosis Virus isolation Blood sample Antibody titre Infection
Neutralizing CRN
Sera from stable L sumo wrestlers
HG32KK 19 July 1993 23 July 1993 15 June 1993 ,4,4 Primary
31 July 1993 ,445
HG33TM 23 July 1993 26 July 1993 15 June 1993 16 64 Non-primary (recurrent HG)
17 December 1993 22 (2
) 128
HG34NM 26 July 1993 26 July 1993 23 July 1993 8 45 (2
) Non-primary (recurrent HG)
HG35HH 23 July 1993 26 July 1993 26 July 1993 ,4,4 Primary
HG36OK 23 July 1993 23 July 1993 23 July 1993 ,4,4 Primary
31 July 1993 ,464
HG37IY 7 August 1993 8 August 1993 4 August 1993 ,4,4 Primary
20 August 1993 ,44
HG38OH 7 September 1993 7 September 1993 7 September 1993 16 90 Non-primary (recurrent HG)
HG39OY 6 May 1994 6 May 1994 2 August 1993 ,4,4 Primary
6 May 1994 ,411
NHG40NT No onset 31 July 1993 ¢32 ¢128 Previously infected
NHG41IT No onset 4 August 1993 ¢32 ¢128 Previously infected
NHG42NM No onset 4 August 1993 ¢32 ¢128 Previously infected
Sera from stable E sumo wrestlers
HG24MT 15 May 1992 15 May 1992 14 May 1992 ,4,4 Primary (first HG)
12 June 1992 ,4,4
HG25SM 14 May 1992 14 May 1992 14 May 1992 ,4,4 Primary (first HG)
12 June 1992 4 16
HG15HK 11 June 1992 11 June 1992 11 June 1992 8 64 Non-primary (recurrent HG)
17 June 1992 8 45
HG16AT 6 August 1993* 6 August 1993* 31 July 1993 8 22 Non-primary (recurrent HG)
*Of the two viruses isolated from case HG16AT, this is the sampling date for isolation of virus HG16AT-D22 (Table 2).
F. Ban and others
2412 Journal of General Virology 89
Table 2. Characteristics of sumo wrestler herpes gladiatorum (HG) cases and HSV-1 isolates
Stable HG case RF of BgK
in wrestler’s
original geographical region*
HSV-1 isolate designation BglII RFLP variant Main lesion site KVE
B HG3MHA Unknown (USA; 21) HG3MHA-D2 BgO
Eyelid 2
HG27KH Low (Kyushu; 20) HG27KH-D14 BgO
Forehead 2
D HG8TM Lower (Chubu-Tohoku; 16) HG8TM-D3 BgK
(D3) Ear +
HG26KY Lower (KantoD; 15) HG26KY-D8 BgK
(D8/21) Cheek 2
HG28AK Lower (Kanto; 19) HG28AK-D21 BgK
(D8/21) Forehead 2
E HG24MT High (Shikoku-Chugoku-Osaka; 15) HG24MT-D6 BgK
(EK) Forehead +
HG25SM Lower (Chubu-Tohoku; 15) HG25SM-D7 BgK
(EK) Forehead +
HG15HK Intermediate (Kyotod; 17) HG15HK-D10 BgK
(EK) Forehead +
HG16AT Tokyo (17) HG16AT-D22 BgK
(EK) Neck +
HG16AT-D25 BgK
(EK) Nape 2
G HG20SK Tokyo (16) HG20SK-D1 BgK
(G) Face +
I HG23TA High (Shikoku-Chugoku-Osaka; 18) HG23TA-D4 BgK
(I) Around the left eye 2
(I) Left eye (conjunctivitis) 2
J HG29SD High (Shikoku-Chugoku-Osaka; 16) HG29SD-D12 Non-BgK
(J) Ear 2
K HG30SS Low (Kyushu; 22) HG30SS-D13 BgK
(EK) Forehead 2
HG31IM Low (Kyushu; 16) HG31IM-D15 BgK
(EK) Forehead/head +
L HG32KK High (Shikoku-Chugoku-Osaka; 15) HG32KK-D16 BgK
(L16-20) Forehead +
HG33TM High (Shikoku-Chugoku-Osaka; 15) HG33TM-D17 Non-BgK
(L17) Eye 2
HG34NM Lower (Kanto; 16) HG34NM-D18 BgK
(L16-20) Armpit 2
HG35HH Lower (Kanto; 18) HG35HH-D19 BgK
(L16-20) Chin +
HG36OK High (Shikoku-Chugoku-Osaka; 15) HG36OK-D20 BgK
(L16-20) Shoulder +
HG37IY Lower (Chubu-Tohoku; 19) HG37IY-D23 nonBgK
(L23) Forehead 2
HG38OH Lower (Kanto; 23) HG38OH-D24 BgK
(L24) Neck 2
HG39OY Intermediate (Kyoto; 15) HG39OY-D26 BgK
(L26) Ear 2
*The geographical region where the sumo wrestler had lived before joining the stable and the wrestler’s age are given in parentheses.
DThe Kanto Region is located between the Chubu and Tohoku Regions and, therefore, within a lower BgK
RF (11 %) area (Ozawa et al., 2006).
dThe Kyoto Prefecture is located between the Shiga Prefecture, a low BgK
RF (27.3 %) area, and the Osaka Prefecture, a high BgK
RF (49.1 %) area (Ozawa et al., 2006). Therefore, the BgK
RF of
Kyoto is denoted as intermediate here.
HSV-1 RFLP variants associated with herpes gladiatorum 2413
all other stables, one HSV-1 strain was responsible for all HG
cases in that stable (Table 2 and data supplements B–G).
Eight different BgK
strains [BgK
(D3), BgK
(EK), BgK
(G), BgK
(I), BgK
(L16–20), BgK
and BgK
(L26)]were isolated from wrestlers in six stables,
one BgO
strain [BgO
(B)]was isolated from two wrestlers
in one stable and three different non-BgK
strains [non-BgK
(J), (L17) and (L23)]were
isolated from wrestlers in two stables (Table 2). These BgK
strains were all the BgK
variant except for BgK
(D3). The number of stables in
which BgK
was isolated (six) was larger than that in which
was isolated (three) (Table 2). Furthermore, for
sumo wrestlers with HG, the BgK
RF value of 81 % (17 of
the 21 BgK
-infected wrestlers with skin or eyelids lesions;
Table 2) was significantly higher (data supplement H) than
the BgK
RF of 27 % in the general population in Japan
(Ozawa et al., 2007).
In seven of the 22 (32 %) HG cases, eczematous lesions
with systemic illness were observed and these cases were
diagnosed as KVE (also called eczema herpeticum)
(Kramer et al., 2004; Marcus et al., 2005; Ruchman,
1954) (Table 2). All HSV-1 isolates from these KVE cases
were BgK
(Table 2).
Concurrent infections of different HSV-1 strains in HG
cases has been suggested previously (Belongia et al., 1991;
Dworkin et al., 1999) but the RFLP data were ambiguous.
The present study is, to our knowledge, the first to report
precise RFLP analyses, with many restriction endonucleases,
of HSV-1 isolates from HG cases. The living conditions of
professional sumo wrestlers suggested that the source of
primary HSV-1 infections among sumo wrestlers in each
stable was their fellow wrestlers. Three different BgK
and two different non-BgK
strains were isolated
from eight HG cases in stable L wrestlers. Five of these cases
were primary HSV-1 infections. These results indicate that
concurrent HSV-1 infections caused by different HSV-1
strains in wrestlers within the same sumo stable are common
(data supplement J).
In the field of sports medicine, recurrent HG has usually
been diagnosed simply based on symptoms and the
wrestler’s medical history (Anderson, 2005; Becker et al.,
1988; Strauss et al., 1989; Turbeville et al., 2006). Sumo
wrestlers’ HG cases were caused by non-primary HSV-1
infections as well as by primary HSV-1 infections. Repeated
HG recurrences within a short period of time and isolation
of HSV-1 isolates with different RFLP patterns from the
same sumo stable suggested reactivation of latent HSV-1
infections in these wrestlers. The frequent severe skin
damage of sumo wrestlers may impair subcutaneous nerve
cells and the strong physiological and mental stress
resulting from their hard practice regime may affect their
immunological status (data supplement I). This may
explain why HG recurred in a number of sumo wresters.
The possibility of an immunological effect is supported by
the results reported here, since wrestlers who did not
develop HG had high titres of neutralizing antibodies
compared with pre-HG sera from wrestlers who were
susceptible to recurrent HG.
The high association of BgK
with sumo wrestlers’ KVE is
statistically significant (P50.03, Fisher’s exact test).
Therefore, a BgK
-related mutation(s) may enhance
HSV-1 pathogenicity in skin or affect the host immuno-
logical response.
Finally, the BgK
RF in professional sumo wrestler HG cases
was higher than that in the general population in Japan; this
difference was statistically significant. In addition, the
number of different BgK
strains isolated from sumo
wrestler HG cases was larger than the number of BgO
and non-BgK
variants isolated from these cases;
the number of stables in which BgK
was isolated was also
larger than that in which non-BgK
was isolated.
Taken together, these results suggest that latent BgK
infections were reactivated and transmitted more efficiently
than latent non-BgK
infections in these cases (data
supplement K). Future studies in this laboratory will
analyse the genome sequences of these BgK
isolates. As far as we are aware, the present study is the
first to suggest that the efficiency of HSV-1 reactivation/
recurrence in humans may depend on the HSV-1 variant
or strain and it supports the BgK
dispersion hypothesis
(Eda et al., 2007; Ozawa et al., 2006, 2007).
We thank Drs S. Okabe, E. Ichikawa and E. Okubo and Doai Kinen
Hospital for contributions to an initial stage of this study and Mr R.
Kitamura for technical assistance.
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HSV-1 RFLP variants associated with herpes gladiatorum 2415
... 32 Restriction endonuclease analysis and sequencing of hypervariable genomic sequences are generally used for the characterization of strains or genogroups. [33][34][35] These methodologies have notably permitted the demonstration of relationships between HSV-1 genotypes and human ethnic groups in the populations of various countries. 36 For instance, in Europe, phylogenetic analyses performed using glycoprotein gene sequences revealed the separation of strains in three genogroups 32,37,38 and revealed homologous recombination as an important feature in the evolution of the HSV-1 genome. ...
... As for the pathogenicity of HSV-1 strains, some variants (identified by means of restriction fragment length polymorphism analysis) have been suspected in a recent study to be of higher virulence when inoculated in animals and to have an increased efficiency of reactivation in human. 34 In our study, no correlation was found between microsatellite markers and the capability to induce BPn. Thus, microsatellite haplotype did not appear to be a predictive diagnosis marker for the severity of the herpetic infection and the outcome of the BPn. ...
According to recent reports, herpes simplex virus type 1 (HSV-1) induces bronchopneumonitis (BPn) in immunocompetent patients undergoing prolonged mechanical ventilation (MV), whose respiratory functions deteriorate with a poor outcome. HSV-1 BPn is associated with HSV symptomatic or symptomless reactivation in the oropharynx. We sought to systematically and genetically characterize HSV-1 strains isolated from immunocompetent patients receiving prolonged MV and to characterize the genetic relationship of strains sequentially isolated from oropharyngeal samples (OPS) and broncho-alveolar liquids (BAL) to determine the natural course of HSV BPn. In this molecular epidemiological study, microsatellite technology was used to determine genetic relationships between 211 HSV-1 strains isolated from OPS and/or BAL from 106 patients receiving MV. Microsatellite haplotypes of HSV-1 strains sequentially isolated from the same individual were identical, and HSV-1 isolates from the lung were genetically indistinguishable from strains isolated from the oral cavity. Each patient was characterized by their own HSV-1 microsatellite haplotype, and no nosocomial transmission of strains between patients was observed. Our results demonstrate that, in patients who receive MV, the HSV-1 pulmonary infection results from the reactivation of genetically related HSV-1 in the oropharynx, which progressively infects the lower respiratory tract.
A 17-year-old male with vesicles on the head, face and neck admitted to our hospital with a diagnosis of Kaposi's varicelliform eruption. Four days later, another member of Judo club of the same high school consulted our hospital for vesicles on the forehead and head, and he also had a fever. Additional two other members presented with vesicles on the head on 10 days later. Because all these patients were members of the same Judo club, we diagnosed as herpes gladiatorum, which is herpes simplex virus infection that transmits byhard physical contact in exercise or game. If herpes simplex infection develops among members of sports club, patients should refrain from training, and to find the other members with early lesions, screening should be performed. As well known in Trichophyton tonsurans infection, it is an effective prevention to ensure awareness of herpes gladiatorum.
The development of sports activities promoted as a health factor should not hide the increased risk for diseases, more particularly infections. A review of articles made over the last 20 years was made with a descriptive epidemiological purpose. The most marked risk is skin infection with methicillin-resistant community acquired Staphylococcus aureus (27.4% of the articles), followed by Tinea corporis and capitis (13.7%), and leptospirosis (11.7%). The risk of blood-borne infection seems low, and articles are rare (3.9%). The risk of disease with respiratory transmission (measles, meningococcal meningitis) must be taken into account. The effect of physical activity on the immune system depends on the type and duration of the work out: it seems to be beneficial for a workout of a moderate intensity, and deleterious for a sustained acute work out, or a period of intensive training. These periods of protection or susceptibility to infections are described as "open window" and "J curve". The only recommendations for prevention of sport-related infections arise from the frequency of skin infections and the severity of blood-borne infections. These recommendations are published by American and international sports authorities. The specificity of athletes' management is due to imperatives of competitiveness (maintaining physical performance) and the necessity of temporary eviction from sports, in case of contagiousness. The athletes must make sure their recommended vaccinations are up-to-date.
Herpes simplex virus type 1 (HSV-1) is the cause of a serious and often fatal encephalitis. Patients who survive herpes simplex encephalitis (HSE) experience behavioral abnormalities including profound cognitive dysfunctions. We have developed a rat model of acute HSE to investigate the cognitive impairments caused by HSV-1 central nervous system (CNS) infection. Following intranasal inoculation of Lewis rats with a neurovirulent strain of HSV-1, animals shed virus in both ocular and nasal secretions and developed clinical signs of infection, including partial complex motor seizures that eventually generalized. Homogenization assays demonstrated infectious virus in the trigeminal ganglia, olfactory bulbs, and the piriform and entorhinal cortices. Histopathological assessment revealed inflammatory and hemorrhagic lesions in the trigeminal ganglia, olfactory bulbs, amygdala, hippocampus, the piriform and entorhinal cortices, and the spinal trigeminal nuclei. Viral antigens and nucleic acids were also detected within these structures by immunofluorescence microscopy and in situ hybridization, respectively. Viral-induced astrocytic hypertrophy in the CNS was demonstrated by glial fibrillary acidic protein immunoreactivity. Together, these results indicate that HSV-1 has the ability to invade, replicate, and induce site-specific CNS damage in the Lewis rat.
Skin infections, both bacterial and viral, are endemic in contact sports such as wrestling and rugby football. In this report, we describe four cases of extensive cutaneous herpes simplex virus in players on a rugby team. All players had a prodrome of fever, malaise, and anorexia with a weight loss of 3.6 to 9.0 kg. Two players experienced ocular lesions associated with cutaneous vesicular lesions of the face. A third player, who had herpetic lesions on his lower extremity, experienced paresthesias, weakness, and intermittent urinary retention and constipation. All infected players on the team were forwards or members of the "scrum," which suggests a field-acquired infection analogous to the herpetic infections seen in wrestlers (herpes gladiatorum). Considering the serious sequelae of recurrent herpes simplex keratitis, the traumatic skin lesions in rugby football players should be cultured for herpes virus, and infected individuals should be restricted from playing until crusted lesions have disappeared.(JAMA 1984;252:533-535)
Early and late sera of rabbits immunized with herpes simplex virus were fractionated into IgG and IgM, and the minimal concentration of complement (C) required for full enhancement of neutralizing activity was determined for each by the plaque reduction method. In tests employing simultaneous mixing of virus, antibody and C, C‐requiring neutralizing (CRN) antibody in IgM required 2–8 times more C than that in IgG. When virus‐antibody mixtures were incubated at 0 C overnight before addition of C, a marked enhancement of CRN endopoint especially of late IgG and IgM was exhibited, in contrast to materially unchanged titers of the ordinary neutralizing antibody. This result suggested an abundance of slow‐reacting CRN‐virus complexes. The CRN antibody so detected required about 4 times more C than that detectable by the usual test in the case of late IgG and IgM. When virus sensitized with late IgG at 0 C overnight was further incubated at 37 C for 1 hr, the C requirement changed but slightly without showing any more increase of the endpoint, whereas sensitization at 0 C for 2 to 3 days further increased the CRN antibody endpoint but the C requirement was equal to that after 1 day's sensitization at 0 C. Based on these and earlier findings, a hypothesis is proposed that binding of a single antibody molecule with virus may cause a series of changes of the virus particle or part of those changes depending on the nature of antibody and on the sensitization condition, and C added to such complexes at an appropriate stage of the changes can accelerate the procession of the changes leading eventually to inactivation.
Daniels (1975) has summarized the neutralization phenomenon as representing 3 pathways: (1) saturation of viral antigens, (2) aggregation by cross-linking of multivalent virions by bivalent antibodies, and (3) virolysis. Although the net result in each case is loss of or reduction in infectivity, the underlying mechanisms may be basically different. Virolysis, for example, is the result of an enveloped virus reacting with antibodies specific for the envelope proteins and depends on participation of the complete complement system. Aggregation may reduce the number of infectious units without literally neutralizing the individal virions. Saturation may or may not involve intrinsic neutralization. In order to understand the fundamental mechanism, it seems preferable to select as a paradigm the simplest available system - a simple virus (e.g., one composed of several copies of one antigen directly accessible to antibody) reacting with a homogeneous population of high-affinity antibody (e.g., late IgG) capable of neutralizing without the aid of accessory substances. Interaction of virus at a very low concentration with the minimum multiplicity of antibody is most likely to reveal why virus has been neutralized. Since under some circumstances neutralized virus can still adsorb to cells, or conversely, since adsorbed virus can still be neutralized, the implication is that the viral capsid has undergone an alteration that subverts subsequent interaction with cells. The nature of the alteration is most likely to be understood on the basis of protein-protein interactions. Some clues have already been described indicating that each reactant has undergone some change from its native state. Antibodies can interact with complement, or bind to cells, only after they have reacted with antigen. Feinstein and Rowe (1965) have proposed that antibody undergoes a conformational rearrangement upon binding to antigen (for an extensive discussion of this proposal see Feinstein et al., 1971). Several examples have been cited that indicate conformational or degradative changes in virion capsids following interaction with antibody. It is of interest that, whereas early antibody reacts with virus but requires mediation, late antibody can neutralize independently. It has also been shown that one difference between early and late antibody is the greater binding affinity of late antibody. The greater the binding affinity, the greater the stress, involvement, and disorganization in the capsid. Such disorganization may be reversible (e.g., by causing dissociation) but in such a state the capsid may not be acceptable to a cell. An attempt has been made in this article to delineate some of the problems: (1) the mechanism of intrinsic neutralization, (2) the single-hit versus multihit requirement for neutralization, (3) the nature of the nonneutralized or sensitized state, (4) the nature of mediated neutralization by complement or antiglobulin, (5) the differences in the characteristics of virus-antibody complexes according to antibody type and affinity. It hardly needs to be stated that solution of these problems will represent the groundwork for considerations of problems at the next level - in vivo interactions.
Digestion of herpes simplex virus DNA by the HinIII or Eco RI restriction endonucleases yielded 11 to 15 fragments with molecular weights between 1 x 10(6) and 28 x10(6). The electrophoretic profiles obtained in 0.3% agarose gels with DNA fragments from none different strains of herpes simplex virus type 1 could be readily differentiated from the patterns exhibited by the corresponding fragments from four separate strains of type 2 virus; however, with each serotype, the laboratory strains differed significantly among themselves and also from isolates passaged a minimum number of times outside the human host. Digestion of all DNAs of herpes simples virus with either enzyme reproducibly generated two classes of fragments (major and minor) which differed in molar ocncentration. Moreover, although the molecular weight of an intact herpes simplex 1(F1) DNA molecule is approximately 98 x 10(6), the summed molecular weights of all major and minor HinIII fragments totalled 160 x 10(6), and the seven major fragments alone accounted for only 60 x 10(6). These unusual features indicate the existence of limited heterogeneity in the positions of cleavage sitet along individual molecules. We have eliminated the possibility that minor fragments arose from contamination with the defective DNA of high byoyant density which appears on serial undiluted passage of the virus. In fact, this latter type of DNA was resistant to cleavage by HinIII and gave large amounts of only two species of EcoRI fragments; suggesting that the defective molecules consist of many tandem repeats of a small segment of viral DNA. The heterogeneity in the viral DNA of normal density appears to be related to the structural organization of the molecules and does not necessarily imply differences in genetic content.