Immune-evasive chemokines

The role of MC148 in MCV immune evasion cannot be determined because there are no suitable animal models of infection. Nevertheless, the ability of MCI48 to inhibit chemokine-mediated responses in vitro (Fig. 2) strongly suggests that this vCK plays a role in preventing an inflammatory response to MCV infection. ... 

From what is known about CMV-encoded chemokines and chemokine receptors, it appears that their participation in immune evasion would be mainly at the level of viral dissemination sheltered from the immune system through (cell-to-cell) passage and movement of receptor bearing infected cells bidirectionally across endothelial barriers. In addition, the ability of pUS28 to withdraw CC chemokines from the environment of infected cells could also confer a measure of immune evasion by blunting effector lymphocyte migration and activation. 

Other chapters in this book), as well as withdrawal of chemokines (Billstrom et al. 1999 Bodaghi et al. 1998 Vieira et al. 1998). These phenomena acting in concert are likely to result in the typical low-profile distribution of virus in the host to contribute to the immune evasion inherent to CMV infection. 

Kirk et al., 2001 Nomura Hasegawa, 2000 Sharma et al., 2013 Tumquist et al., 2007). Incorporating therapeutic chemokines and other cytokines as adjuncts in immunotherapy protocols for cancer treatment has been efficacious in alleviating tumor immune evasion and increasing survival (Ardolino, Hsu, Raulet, 2015 Wennerberg, Kremer, Childs, Lundqvist, 2015). 

Analysis of the genomes of HHV-6, HHV-8, murine CMV, and Molluscum contagiosum virus types 1 and 2 (MCV-1 and MCV-2) has identified ORFs with significant sequence similarity to chemokines (Table 1). There is increasing experimental evidence that the proteins encoded by these ORFs are used for immune evasion through blockade of normal signaling by host chemokines. The following discussion focuses on the examples for which functional analysis has been reported. 

The use of viral chemokine/receptor mimics and inhibitors identified in particular virus families such as herpesviruses, poxviruses and HIV indicates their importance in pathogensis of these viruses, either for evasion of the immune response as with poxviruses and herpesviruses or addtionally the use of recptors for viral entry as with HIV and poxviruses. Further studies will almost certainly identify a greater range of viruses producing such mimics. 

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