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Smutty tale
COMMENT Horizons N8WCJOStdll urvcillance in the UK since May 1990 has recently idmtified ten atypical cases of Creutafeldt-Jakob disease (CJD) out of a total of 185 cases of CJD in this period. All ten occurred in relatively young people (ages currently or at time of death between 18 and 41 years, compared with the average age of onset of CJD of 65 years); very few cases of CJD among peopk in this age group occurred worldwide before 1990. These patients had a relatively protracted disease, with an average of 12 months between disease onset
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ThehIckyfew7
ome people seem to escape HIV internon despite repeated sexual conract with HIV-l-infected pawners. Are mc‘se people just lucky or are they resistant to HIV-l mfec tion? Pa*.ton and coworkers have sn:died 2S apparently HIV-nepativc pcwple who reported multiple sexual contacts with HIV-i&cted partncm. They tested how easily CD4’ lymphocytes from these people could be infected with HIV-1 in vitro. Although some people in this group had lymphocytes that were infected as easily as control cells, others had lymphocytes that were relatively resistant to infection with primary isolates of HIV (although not to T-cell-
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HlaBdheaon ontypeable Haemophih injluenzue colonize the upper respiratory tract and cause various diseases, including otitis media and bron&i& As well as haemagglutinsting pili, the bacterial mole.cuks involved in colonization include two high-molecular-mass surface adhesins, HMWl and HMW2, which mediate attachment to epithelial cells. Members of this family occur in 70-75% of nonty ble H. inf7nenzue strain% yet tr e remaining strains still adhere strongly in vitro. Barenlcamp and St Ceme identified ahighlyimmwogcnich lar-mawsurfnccprotcin 7iiz!ri swain,expnzssiondwhichalknved
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and death,compared with 4 months for typical CJD. They also had atypical symptoms, predominantly involving behavioural disturbances and ataxia, rather than dementia. A novel and characteristic neuropathological pattern was identified, with plaques of prion protein resembling those seen in kuru and scrapie; such plaques are rare in CJD patients. These ten cases probahl) represent a new form of CJD, which might be caused by a new strain of prion. One plausible explnr?ltion is that the disease variant results from exposure to the bovine spongifor.:l adapted strains). Resistance could be overcome by certain mutations within the envelope glycoprotein. and was not related to reduced levels of surface CD4. Resistant cells produced more of the C-C cytokines RANTES, MIP-la and MIP-18. Such CD4’ cell resistance might at least partially protect the individual from HIV infection, although it is unlikely to be the only mechanism involved. Paxton. %‘..I. et ;~f. (1096) Relative resistance to HIV-I infectmn of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual CX~~NUTS. N~~furc Med. 2.
412-417 nonadherent Escherichia colt’ to adhere to Chang epithelial cells. Mutants in this locus (termed hia) had much reduced attachment to epithelial cells in vitro. The hia locus seems to be present in most nontypeabk H. influenzae strains that do not express HMW l/HMWZ-like proteins; hence, if Hia proves to be important for colonization in humans, it might be a plausible vaccine candidate. Barcnkamp,
SJ. and St Cane,
J.W.,
ily of high-molecular-weight adhesion proteins expres& by non-typable Md.
Micro-
Will. R.G. et .a/. I lY96) A new of Crcurx.feldt-Jakoh disease UK. la~cc~347. 921-925
vanam in the
-uttyw
hc corn smut fungus Ustihgo nwydis has a highly complex life cycle involving two mating types, a and 6, and a switch between yeastlike forms and filamentous pathogenic forms. The a locus encodes a pheromone system, while h encodes two homeodotGn proteins. The expression of all the genes in the a and h loci is turned on by a Fheromone. Hamnann and colleagues have cloned a gene, prfl, with similarity to the HMG DNA-binding proteins, the product oi which binds specifically to pheromone-response elements located near the a and b loci. Mutants in prff are sterile and do not transcribe the u and 6 loci, suggesting that Prfl mediates the pheromone response. Unexpectedly, although parhogenicity does not seem to involve response to pheromones, such mutants are also nonpathogenie. Pathogenicity can be restored by constitutive expression of the 6 genes, suggesting that low levels of the b products regulate the expression of genes needed for pathogen&y. Its presence at the centre of various signalling pathways might allow Prfl to coordinate the developmental response of the fungus to different stimuli.
T
LU
(19%) Identification of a second fam-
Haemopbihu intluenzoe, bid. 19,12lS-1223
cncPphalopathy (BSE) agent from eating BSE-Infected kef. Although this hypothesis is currently causing considerable alarm in the UK, there is at present no direct evidence for such a link, and only a few of the patients had any contaQ with butchery or diar) farming. It is also unclear why the disease only occurs in the young; increased susceptibility or increased exposure might be involved.
Harm~a~~, H.A.., Kabmalm,R.Md B6auY.
M. (1996)
The phcromnc
cc-
spome factor coordinates tilomeinous growth and pathogenieity in Ustifugo maydis,
EMBOJ.
15.1632~1641
S
ThehIckyfew7
ome people seem to escape HIV internon despite repeated sexual conract with HIV-l-infected pawners. Are mc‘se people just lucky or are they resistant to HIV-l mfec tion? Pa*.ton and coworkers have sn:died 2S apparently HIV-nepativc pcwple who reported multiple sexual contacts with HIV-i&cted partncm. They tested how easily CD4’ lymphocytes from these people could be infected with HIV-1 in vitro. Although some people in this group had lymphocytes that were infected as easily as control cells, others had lymphocytes that were relatively resistant to infection with primary isolates of HIV (although not to T-cell-
S
HlaBdheaon ontypeable Haemophih injluenzue colonize the upper respiratory tract and cause various diseases, including otitis media and bron&i& As well as haemagglutinsting pili, the bacterial mole.cuks involved in colonization include two high-molecular-mass surface adhesins, HMWl and HMW2, which mediate attachment to epithelial cells. Members of this family occur in 70-75% of nonty ble H. inf7nenzue strain% yet tr e remaining strains still adhere strongly in vitro. Barenlcamp and St Ceme identified ahighlyimmwogcnich lar-mawsurfnccprotcin 7iiz!ri swain,expnzssiondwhichalknved
N
and death,compared with 4 months for typical CJD. They also had atypical symptoms, predominantly involving behavioural disturbances and ataxia, rather than dementia. A novel and characteristic neuropathological pattern was identified, with plaques of prion protein resembling those seen in kuru and scrapie; such plaques are rare in CJD patients. These ten cases probahl) represent a new form of CJD, which might be caused by a new strain of prion. One plausible explnr?ltion is that the disease variant results from exposure to the bovine spongifor.:l adapted strains). Resistance could be overcome by certain mutations within the envelope glycoprotein. and was not related to reduced levels of surface CD4. Resistant cells produced more of the C-C cytokines RANTES, MIP-la and MIP-18. Such CD4’ cell resistance might at least partially protect the individual from HIV infection, although it is unlikely to be the only mechanism involved. Paxton. %‘..I. et ;~f. (1096) Relative resistance to HIV-I infectmn of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual CX~~NUTS. N~~furc Med. 2.
412-417 nonadherent Escherichia colt’ to adhere to Chang epithelial cells. Mutants in this locus (termed hia) had much reduced attachment to epithelial cells in vitro. The hia locus seems to be present in most nontypeabk H. influenzae strains that do not express HMW l/HMWZ-like proteins; hence, if Hia proves to be important for colonization in humans, it might be a plausible vaccine candidate. Barcnkamp,
SJ. and St Cane,
J.W.,
ily of high-molecular-weight adhesion proteins expres& by non-typable Md.
Micro-
Will. R.G. et .a/. I lY96) A new of Crcurx.feldt-Jakoh disease UK. la~cc~347. 921-925
vanam in the
-uttyw
hc corn smut fungus Ustihgo nwydis has a highly complex life cycle involving two mating types, a and 6, and a switch between yeastlike forms and filamentous pathogenic forms. The a locus encodes a pheromone system, while h encodes two homeodotGn proteins. The expression of all the genes in the a and h loci is turned on by a Fheromone. Hamnann and colleagues have cloned a gene, prfl, with similarity to the HMG DNA-binding proteins, the product oi which binds specifically to pheromone-response elements located near the a and b loci. Mutants in prff are sterile and do not transcribe the u and 6 loci, suggesting that Prfl mediates the pheromone response. Unexpectedly, although parhogenicity does not seem to involve response to pheromones, such mutants are also nonpathogenie. Pathogenicity can be restored by constitutive expression of the 6 genes, suggesting that low levels of the b products regulate the expression of genes needed for pathogen&y. Its presence at the centre of various signalling pathways might allow Prfl to coordinate the developmental response of the fungus to different stimuli.
T
LU
(19%) Identification of a second fam-
Haemopbihu intluenzoe, bid. 19,12lS-1223
cncPphalopathy (BSE) agent from eating BSE-Infected kef. Although this hypothesis is currently causing considerable alarm in the UK, there is at present no direct evidence for such a link, and only a few of the patients had any contaQ with butchery or diar) farming. It is also unclear why the disease only occurs in the young; increased susceptibility or increased exposure might be involved.
Harm~a~~, H.A.., Kabmalm,R.Md B6auY.
M. (1996)
The phcromnc
cc-
spome factor coordinates tilomeinous growth and pathogenieity in Ustifugo maydis,
EMBOJ.
15.1632~1641