Targeting herpesvirus entry complex and fusogen glycoproteins with prophylactic and therapeutic agents

Zhong, L.; Zhang, Wanlin; Krummenacher, Claude; Chen, Yixin; Zheng, Qingbing; Zhao, Qinjian; Zeng, Mu‐Sheng; Xia, Ningshao; Zeng, Yi‐Xin; Xu, Miao; Zhang, Xiao

doi:10.1016/j.tim.2023.03.001

Cited by 16 publications

(15 citation statements)

References 117 publications

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“…Since (maternal) antibodies are considered to play a crucial role in protection against EEHV-HD [ 2 , 3 , 5 ] and gH/gL is an important target of the neutralizing antibody response against many herpesviruses [ 19 , 20 , 21 , 22 , 23 ], it is highly plausible that the EEHV-specific gH/gL-directed antibody response does not only correlate with but also plays a direct role in protection against EEHV-HD. For all EEHV-HD fatalities tested, normalized gH/gL ΔOD values specific for the HD-causing EEHV (sub)species were always below 0.23 in the last sample taken before the onset of disease ( Figure 8 ).…”

Section: Resultsmentioning

confidence: 99%

“…Both gB and gH/gL are conserved between all herpesviruses, essential for herpesvirus infections, and major targets of the neutralizing immune response against many herpesviruses, and therefore, both proteins are considered prime candidates for anti-herpesvirus vaccine development [ 19 , 20 , 21 , 22 , 23 ]. Most current efforts to develop an EEHV-HD vaccine make use of gB, the viral fusion protein, as the vaccine antigen [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to gB, antibody responses to EEHV antigens gH/gL as well as ORF-Q [ 2 ] were found to correlate well with protection against EEHV-HD. As gH/gL is known to have an important role in infection of all herpesviruses, being involved in receptor recognition and gB activation [ 19 ], while the function of ORF-Q is unknown, we believe gH/gL should be considered the prime candidate antigen for EEHV-HD vaccine design.…”

Section: Discussionmentioning

confidence: 99%

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Low gH/gL (Sub)Species-Specific Antibody Levels Indicate Elephants at Risk of Fatal Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease

Hoornweg,

Schaftenaar,

Rutten

et al. 2024

Viruses

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Elephant endotheliotropic herpesviruses (EEHVs), of which eleven (sub)species are currently distinguished, infect either Asian (Elephas maximus) or African elephants (Loxodonta species). While all adult elephants are latently infected with at least one EEHV (sub)species, young elephants, specifically those with low to non-detectable EEHV-specific antibody levels, may develop fatal hemorrhagic disease (EEHV-HD) upon infection. However, animals with high antibody levels against EEHV(1A) gB, an immunodominant antigen recognized by antibodies elicited against multiple (sub)species, may also occasionally succumb to EEHV-HD. To better define which animals are at risk of EEHV-HD, gB and gH/gL ELISAs were developed for each of the Asian elephant EEHV subspecies and assessed using 396 sera from 164 Asian elephants from European zoos. Antibody levels measured against gB of different (sub)species correlated strongly with one another, suggesting high cross-reactivity. Antibody levels against gH/gL of different subspecies were far less correlated and allowed differentiation between these (sub)species. Importantly, while high gB-specific antibody levels were detected in the sera of several EEHV-HD fatalities, all fatalities (n = 23) had low antibody levels against gH/gL of the subspecies causing disease. Overall, our data indicate that (sub)species-specific gH/gL ELISAs can be used to identify animals at risk of EEHV-HD when infected with a particular EEHV (sub)species.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Low gH/gL (Sub)Species-Specific Antibody Levels Indicate Elephants at Risk of Fatal Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease

Hoornweg,

Schaftenaar,

Rutten

et al. 2024

Viruses

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“…Conversely, complementation failed in other cases, including the substitution of gB in a BoHV-4 gB-null mutant by a homologous glycoprotein from vesicular stomatitis virus (VSV) [ 13 , 14 , 15 ]. Additionally, viral glycoproteins, including gB, have been considered as vaccine targets for various herpesviruses [ 16 ]. Thus, exploring heterologous protein expression and functional complementation among viral glycoproteins offers a potential avenue for designing viral-vectored vaccines, wherein a non-pathogenic virus could serve as the carrier for the vaccine target.…”

Section: Introductionmentioning

confidence: 99%

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant

Moré,

Baker,

Shringi

et al. 2024

Pathogens

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Ovine herpesvirus 2 (OvHV-2) and bovine herpesvirus 4 (BoHV-4) are gamma herpesviruses that belong to the genera Macavirus and Rhadinovirus, respectively. As with all herpesviruses, both OvHV-2 and BoHV-4 express glycoprotein B (gB), which plays an essential role in the infection of host cells. In that context, it has been demonstrated that a BoHV-4 gB-null mutant is unable to infect host cells. In this study, we used homologous recombination to insert OvHV-2 ORF 8, encoding gB, into the BoHV-4 gB-null mutant genome, creating a chimeric BoHV-4 virus carrying and expressing OvHV-2 gB (BoHV-4∆gB/OvHV-2-gB) that was infectious and able to replicate in vitro. We then evaluated BoHV-4∆gB/OvHV-2-gB as a potential vaccine candidate for sheep-associated malignant catarrhal fever (SA-MCF), a fatal disease of ungulates caused by OvHV-2. Using rabbits as a laboratory model for MCF, we assessed the safety, immunogenicity, and efficacy of BoHV-4∆gB/OvHV-2-gB in an immunization/challenge trial. The results showed that while BoHV-4∆gB/OvHV-2-gB was safe and induced OvHV-2 gB-specific humoral immune responses, immunization conferred only 28.5% protection upon challenge with OvHV-2. Therefore, future studies should focus on alternative strategies to express OvHV-2 proteins to develop an effective vaccine against SA-MCF.

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“…EBV primarily infects two types of host cells, B cells and epithelial cells, 9 , 10 through a complex, multistep process involving several viral glycoproteins. 11 , 12 At least five reported EBV glycoproteins (gp350/220, gH, gL, gp42, and gB) are involved in the viral entry process, 13 of which four (gH, gL, gp42, and gB) and three (gH, gL, and gB) are indispensable for membrane fusion with B cells and epithelial cells, respectively. 14 The gHgL heterodimer, comprising membrane anchor gH and soluble gL, 15 is an important component of the EBV entry complex and, together with gB, forms the core fusion machinery that participates in EBV infection within both host cell types.…”

Section: Introductionmentioning

confidence: 99%

Targeting herpesvirus entry complex and fusogen glycoproteins with prophylactic and therapeutic agents

Cited by 16 publications

References 117 publications

Low gH/gL (Sub)Species-Specific Antibody Levels Indicate Elephants at Risk of Fatal Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease

Low gH/gL (Sub)Species-Specific Antibody Levels Indicate Elephants at Risk of Fatal Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant

Non-overlapping epitopes on the gHgL-gp42 complex for the rational design of a triple-antibody cocktail against EBV infection

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